COG7-congenital disorder of glycosylation is a rare autosomal recessive congenital disorder of glycosylation caused by biallelic COG7 variants. COG7 deficiency impairs conserved oligomeric Golgi complex integrity, disrupts Golgi trafficking, and causes combined N- and O-glycosylation defects with severe infantile multisystem disease that can include progressive microcephaly, hypotonia, growth failure, gastrointestinal pseudo-obstruction, ventricular septal defect, wrinkled skin, adducted thumbs, and recurrent hyperthermia.
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name: COG7-congenital disorder of glycosylation
creation_date: "2026-05-09T12:45:18Z"
updated_date: "2026-05-20T03:06:34Z"
description: >-
COG7-congenital disorder of glycosylation is a rare autosomal recessive
congenital disorder of glycosylation caused by biallelic COG7 variants.
COG7 deficiency impairs conserved oligomeric Golgi complex integrity,
disrupts Golgi trafficking, and causes combined N- and O-glycosylation
defects with severe infantile multisystem disease that can include
progressive microcephaly, hypotonia, growth failure, gastrointestinal
pseudo-obstruction, ventricular septal defect, wrinkled skin, adducted
thumbs, and recurrent hyperthermia.
category: Mendelian
disease_term:
preferred_term: COG7-congenital disorder of glycosylation
term:
id: MONDO:0012118
label: COG7-congenital disorder of glycosylation
parents:
- congenital disorder of glycosylation type II
- developmental anomaly of metabolic origin
- defect in conserved oligomeric Golgi complex
synonyms:
- COG7-CDG
- COG-7 deficiency
- CDG type IIe
- CDG-IIe
inheritance:
- name: Autosomal recessive inheritance
inheritance_term:
preferred_term: Autosomal recessive inheritance
term:
id: HP:0000007
label: Autosomal recessive inheritance
description: >-
The initial COG7-CDG report described affected siblings, and the disorder is
modeled as an autosomal recessive COG-complex deficiency.
evidence:
- reference: PMID:15107842
reference_title: Mutation of the COG complex subunit gene COG7 causes a lethal congenital disorder.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Here we describe two siblings with a fatal form of CDG caused by a
mutation in the gene encoding COG-7, a subunit of the conserved
oligomeric Golgi (COG) complex.
explanation: >-
The sibling report and causal COG7 mutation support a familial Mendelian
disorder; the inheritance mode is captured by the MONDO/OMIM disease
concept and Falcon report.
pathophysiology:
- name: COG7 Loss Destabilizes the Conserved Oligomeric Golgi Complex
description: >-
COG7 variants impair integrity of the conserved oligomeric Golgi complex,
disturbing intra-Golgi trafficking and the localization of glycosylation
machinery.
genes:
- preferred_term: COG7
term:
id: hgnc:18622
label: COG7
biological_processes:
- preferred_term: Golgi vesicle transport
modifier: ABNORMAL
term:
id: GO:0048193
label: Golgi vesicle transport
- preferred_term: intra-Golgi vesicle-mediated transport
modifier: ABNORMAL
term:
id: GO:0006891
label: intra-Golgi vesicle-mediated transport
locations:
- preferred_term: Golgi apparatus
term:
id: GO:0005794
label: Golgi apparatus
evidence:
- reference: PMID:15107842
reference_title: Mutation of the COG complex subunit gene COG7 causes a lethal congenital disorder.
supports: SUPPORT
evidence_source: IN_VITRO
snippet: >-
The mutation impairs integrity of the COG complex and alters Golgi
trafficking, resulting in disruption of multiple glycosylation pathways.
explanation: >-
This directly supports the upstream COG-complex and Golgi-trafficking
defect.
downstream:
- target: Mislocalized Golgi Glycosylation Machinery
description: >-
Loss of COG-complex integrity disrupts Golgi trafficking and enzyme
compartmentalization, mislocalizing glycosylation machinery.
causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
evidence:
- reference: PMID:15107842
reference_title: Mutation of the COG complex subunit gene COG7 causes a lethal congenital disorder.
supports: SUPPORT
evidence_source: IN_VITRO
snippet: >-
The mutation impairs integrity of the COG complex and alters Golgi
trafficking, resulting in disruption of multiple glycosylation
pathways.
explanation: >-
The causal COG7 mutation directly links impaired COG-complex integrity
with altered Golgi trafficking and downstream glycosylation disruption.
- reference: PMID:17904886
reference_title: Deficiencies in subunits of the Conserved Oligomeric Golgi (COG) complex define a novel group of Congenital Disorders of Glycosylation.
supports: SUPPORT
evidence_source: OTHER
snippet: >-
If the balance is disturbed, the glycosylation machinery is
mislocalized, which can cause Congenital Disorders of Glycosylation type
II (CDG-II), as illustrated by the identification of congenital defects
in the Conserved Oligomeric Golgi (COG) complex in humans.
explanation: >-
The review explicitly connects COG-complex defects with mislocalized
glycosylation machinery.
- name: Mislocalized Golgi Glycosylation Machinery
description: >-
Disturbed anterograde and retrograde Golgi trafficking mislocalizes
glycosylation enzymes, producing defective glycoprotein maturation.
cell_types:
- preferred_term: fibroblast
term:
id: CL:0000057
label: fibroblast
biological_processes:
- preferred_term: N-glycan processing
modifier: DECREASED
term:
id: GO:0006491
label: N-glycan processing
- preferred_term: Golgi vesicle transport
modifier: ABNORMAL
term:
id: GO:0048193
label: Golgi vesicle transport
- preferred_term: intra-Golgi vesicle-mediated transport
modifier: ABNORMAL
term:
id: GO:0006891
label: intra-Golgi vesicle-mediated transport
locations:
- preferred_term: Golgi apparatus
term:
id: GO:0005794
label: Golgi apparatus
evidence:
- reference: PMID:17904886
reference_title: Deficiencies in subunits of the Conserved Oligomeric Golgi (COG) complex define a novel group of Congenital Disorders of Glycosylation.
supports: SUPPORT
evidence_source: OTHER
snippet: >-
If the balance is disturbed, the glycosylation machinery is mislocalized,
which can cause Congenital Disorders of Glycosylation type II (CDG-II), as
illustrated by the identification of congenital defects in the Conserved
Oligomeric Golgi (COG) complex in humans.
explanation: >-
The review links disturbed vesicular balance to mislocalized
glycosylation machinery in COG-related CDG-II.
- reference: PMID:17904886
reference_title: Deficiencies in subunits of the Conserved Oligomeric Golgi (COG) complex define a novel group of Congenital Disorders of Glycosylation.
supports: PARTIAL
evidence_source: OTHER
snippet: "We collected findings from different COG deficient cell types, such as CHO, yeast and human fibroblasts to hypothesize about structure and function of the COG complex"
explanation: >-
This supports fibroblasts as one human cellular context used to study COG
complex deficiency.
downstream:
- target: Combined N- and O-glycosylation Defect
description: >-
Mislocalized Golgi enzymes impair maturation of both N-linked and
O-linked glycoproteins.
causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
evidence:
- reference: PMID:17904886
reference_title: Deficiencies in subunits of the Conserved Oligomeric Golgi (COG) complex define a novel group of Congenital Disorders of Glycosylation.
supports: SUPPORT
evidence_source: OTHER
snippet: >-
If the balance is disturbed, the glycosylation machinery is
mislocalized, which can cause Congenital Disorders of Glycosylation type
II (CDG-II), as illustrated by the identification of congenital defects
in the Conserved Oligomeric Golgi (COG) complex in humans.
explanation: >-
The review connects disturbed Golgi trafficking balance and
mislocalized glycosylation machinery to COG-related CDG-II.
- reference: PMID:17904886
reference_title: Deficiencies in subunits of the Conserved Oligomeric Golgi (COG) complex define a novel group of Congenital Disorders of Glycosylation.
supports: SUPPORT
evidence_source: OTHER
snippet: >-
COG defects are a novel group of CDG-II with deficient N- as well as
O-glycosylation.
explanation: >-
The same review specifically supports combined N- and O-glycosylation
deficiency in COG defects.
- name: Combined N- and O-glycosylation Defect
description: >-
COG7-CDG produces a type II CDG biochemical pattern with defective
N-glycosylation and O-glycosylation.
biological_processes:
- preferred_term: N-glycan processing
modifier: DECREASED
term:
id: GO:0006491
label: N-glycan processing
- preferred_term: protein O-linked glycosylation
modifier: DECREASED
term:
id: GO:0006493
label: protein O-linked glycosylation
chemical_entities:
- preferred_term: N-glycan
term:
id: CHEBI:59520
label: N-glycan
modifier: ABNORMAL
- preferred_term: O-glycan
term:
id: CHEBI:59521
label: O-glycan
modifier: ABNORMAL
- preferred_term: sialic acid
term:
id: CHEBI:26667
label: sialic acid
modifier: DECREASED
evidence:
- reference: PMID:17904886
reference_title: Deficiencies in subunits of the Conserved Oligomeric Golgi (COG) complex define a novel group of Congenital Disorders of Glycosylation.
supports: SUPPORT
evidence_source: OTHER
snippet: >-
COG defects are a novel group of CDG-II with deficient N- as well as
O-glycosylation.
explanation: >-
This supports combined N- and O-glycosylation defects as the downstream
biochemical consequence.
- reference: PMID:17356545
reference_title: A common mutation in the COG7 gene with a consistent phenotype including microcephaly, adducted thumbs, growth retardation, VSD and episodes of hyperthermia.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
A combined disorder in the biosynthesis of N- and O-linked glycosylation
with hyposialylation was detected.
explanation: >-
This later human series directly supports the combined N- and
O-glycosylation defect with hyposialylation in COG7-CDG.
downstream:
- target: Neurodevelopmental and growth involvement
description: >-
The combined Golgi glycosylation defect is associated with progressive
microcephaly, hypotonia, growth retardation, and failure to thrive in
reported COG7-CDG patients.
causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
evidence:
- reference: PMID:17356545
reference_title: A common mutation in the COG7 gene with a consistent phenotype including microcephaly, adducted thumbs, growth retardation, VSD and episodes of hyperthermia.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The siblings and an unrelated single child of consanguineous parents
presented with growth retardation, progressive, severe microcephaly,
hypotonia, adducted thumbs, feeding problems by gastrointestinal
pseudo-obstruction, failure to thrive, cardiac anomalies, wrinkled skin
and episodes of extreme hyperthermia.
explanation: >-
The COG7 clinical series directly reports neurodevelopmental and growth
manifestations in affected patients with the combined glycosylation
disorder.
- target: Gastrointestinal dysmotility and feeding involvement
description: >-
COG7-CDG patients can have feeding problems from gastrointestinal
pseudo-obstruction, contributing to failure to thrive.
causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
evidence:
- reference: PMID:17356545
reference_title: A common mutation in the COG7 gene with a consistent phenotype including microcephaly, adducted thumbs, growth retardation, VSD and episodes of hyperthermia.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The siblings and an unrelated single child of consanguineous parents
presented with growth retardation, progressive, severe microcephaly,
hypotonia, adducted thumbs, feeding problems by gastrointestinal
pseudo-obstruction, failure to thrive, cardiac anomalies, wrinkled skin
and episodes of extreme hyperthermia.
explanation: >-
The same clinical series reports feeding problems by gastrointestinal
pseudo-obstruction and failure to thrive in COG7-CDG.
- target: Cardiac and thermoregulatory involvement
description: >-
The COG7-CDG multisystem phenotype includes cardiac anomalies and
episodes of extreme hyperthermia.
causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
evidence:
- reference: PMID:17356545
reference_title: A common mutation in the COG7 gene with a consistent phenotype including microcephaly, adducted thumbs, growth retardation, VSD and episodes of hyperthermia.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The siblings and an unrelated single child of consanguineous parents
presented with growth retardation, progressive, severe microcephaly,
hypotonia, adducted thumbs, feeding problems by gastrointestinal
pseudo-obstruction, failure to thrive, cardiac anomalies, wrinkled skin
and episodes of extreme hyperthermia.
explanation: >-
The clinical series directly reports cardiac anomalies and extreme
hyperthermia episodes in COG7-CDG.
- target: Skin involvement
description: Wrinkled skin is reported as part of the COG7-CDG phenotype.
causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
evidence:
- reference: PMID:17356545
reference_title: A common mutation in the COG7 gene with a consistent phenotype including microcephaly, adducted thumbs, growth retardation, VSD and episodes of hyperthermia.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The siblings and an unrelated single child of consanguineous parents
presented with growth retardation, progressive, severe microcephaly,
hypotonia, adducted thumbs, feeding problems by gastrointestinal
pseudo-obstruction, failure to thrive, cardiac anomalies, wrinkled skin
and episodes of extreme hyperthermia.
explanation: >-
Wrinkled skin is directly reported in the same COG7-CDG clinical
series.
- target: Congenital limb involvement
description: >-
COG7-CDG patients can have adducted thumbs as a congenital limb
manifestation.
causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
evidence:
- reference: PMID:17356545
reference_title: A common mutation in the COG7 gene with a consistent phenotype including microcephaly, adducted thumbs, growth retardation, VSD and episodes of hyperthermia.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The siblings and an unrelated single child of consanguineous parents
presented with growth retardation, progressive, severe microcephaly,
hypotonia, adducted thumbs, feeding problems by gastrointestinal
pseudo-obstruction, failure to thrive, cardiac anomalies, wrinkled skin
and episodes of extreme hyperthermia.
explanation: >-
Adducted thumbs are directly reported among the characteristic clinical
findings in the COG7-CDG series.
- target: Abnormal Glycosylation
description: >-
Deficient N- and O-glycosylation produces abnormal glycoprotein
glycosylation profiles.
causal_link_type: DIRECT
evidence:
- reference: PMID:17904886
reference_title: Deficiencies in subunits of the Conserved Oligomeric Golgi (COG) complex define a novel group of Congenital Disorders of Glycosylation.
supports: SUPPORT
evidence_source: OTHER
snippet: >-
COG defects are a novel group of CDG-II with deficient N- as well as
O-glycosylation.
explanation: >-
The review directly supports abnormal glycosylation as the biochemical
manifestation of deficient N- and O-glycosylation in COG defects.
- target: Type II-like serum transferrin isoelectric focusing pattern
description: >-
Defective N-glycan processing is reflected by a type II-like
sialotransferrin isoelectric focusing pattern.
causal_link_type: DIRECT
evidence:
- reference: PMID:16151902
reference_title: Clinical and biochemical presentation of siblings with COG-7 deficiency, a lethal multiple O- and N-glycosylation disorder.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Isoelectric focusing of serum sialotransferrins showed a type 2-like
CDG pattern.
explanation: >-
Serum sialotransferrin IEF is a direct biochemical readout of the
N-glycosylation component of the combined glycosylation defect.
- target: Hyposialylated apolipoprotein C-III isoforms
description: >-
Defective O-glycosylation is reflected by increased hyposialylated
apolipoprotein C-III isoforms.
causal_link_type: DIRECT
evidence:
- reference: PMID:16151902
reference_title: Clinical and biochemical presentation of siblings with COG-7 deficiency, a lethal multiple O- and N-glycosylation disorder.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
O-Glycosylation was investigated by isoelectric focusing of
apolipoprotein C-III, which showed increased fractions of hyposialylated
isoforms.
explanation: >-
Apolipoprotein C-III IEF directly reports the O-glycosylation arm of
the combined biochemical defect.
- target: Decreased total plasma sialic acid
description: >-
Global Golgi glycosylation disruption is reflected by markedly decreased
total plasma sialic acid.
causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
evidence:
- reference: PMID:16151902
reference_title: Clinical and biochemical presentation of siblings with COG-7 deficiency, a lethal multiple O- and N-glycosylation disorder.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "total sialic acid in plasma was strongly decreased"
explanation: >-
Decreased total plasma sialic acid is a directly reported biochemical
consequence in affected siblings with the multiple Golgi glycosylation
defect.
- target: Increased plasma lysosomal enzyme activities
description: >-
The multiple Golgi glycosylation and trafficking defect is accompanied by
increased plasma lysosomal enzyme activities.
causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
evidence:
- reference: PMID:16151902
reference_title: Clinical and biochemical presentation of siblings with COG-7 deficiency, a lethal multiple O- and N-glycosylation disorder.
supports: PARTIAL
evidence_source: HUMAN_CLINICAL
snippet: "Increased activities of lysosomal enzymes in plasma were found"
explanation: >-
Increased plasma lysosomal enzyme activities are reported in affected
siblings with the multiple Golgi glycosylation defect, but the abstract
does not define the exact intermediate mechanism.
- target: Abnormal facial shape
description: >-
Severe multisystem COG7-CDG can include dysmorphic facial appearance as
part of the congenital presentation.
causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
evidence:
- reference: PMID:16151902
reference_title: Clinical and biochemical presentation of siblings with COG-7 deficiency, a lethal multiple O- and N-glycosylation disorder.
supports: PARTIAL
evidence_source: HUMAN_CLINICAL
snippet: "We report on two dysmorphic siblings with severe liver disease who died at the age of a few weeks."
explanation: >-
The sibling report directly documents dysmorphism in COG7-CDG; the
broad HPO facial-shape term is used because no more specific facial
gestalt is given in the abstract.
- target: Severe Liver Disease
description: >-
Multisystem glycoprotein biosynthesis defects contribute to severe
infantile liver disease.
causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
evidence:
- reference: PMID:16151902
reference_title: Clinical and biochemical presentation of siblings with COG-7 deficiency, a lethal multiple O- and N-glycosylation disorder.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
We report on two dysmorphic siblings with severe liver disease who died
at the age of a few weeks.
explanation: >-
Human sibling cases with COG7-related combined glycosylation defects
directly support severe infantile liver disease as a clinical
consequence.
- target: Fatal Infantile Course
description: >-
The severe multiple Golgi glycosylation defect produced an early lethal
infantile presentation in the original affected siblings.
causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
evidence:
- reference: PMID:16151902
reference_title: Clinical and biochemical presentation of siblings with COG-7 deficiency, a lethal multiple O- and N-glycosylation disorder.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "We report on two dysmorphic siblings with severe liver disease who died at the age of a few weeks."
explanation: >-
The clinical report links COG7-CDG with severe liver disease and death
in the first weeks of life.
- name: Neurodevelopmental and growth involvement
description: >-
COG7-CDG multisystem disease includes growth retardation, progressive
severe microcephaly, hypotonia, and failure to thrive.
evidence:
- reference: PMID:17356545
reference_title: A common mutation in the COG7 gene with a consistent phenotype including microcephaly, adducted thumbs, growth retardation, VSD and episodes of hyperthermia.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The siblings and an unrelated single child of consanguineous parents
presented with growth retardation, progressive, severe microcephaly,
hypotonia, adducted thumbs, feeding problems by gastrointestinal
pseudo-obstruction, failure to thrive, cardiac anomalies, wrinkled skin
and episodes of extreme hyperthermia.
explanation: >-
The later COG7 series directly reports neurodevelopmental and growth
manifestations in affected patients.
downstream:
- target: Progressive microcephaly
description: >-
Progressive severe microcephaly is part of the characteristic COG7-CDG
phenotype.
causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
evidence:
- reference: PMID:17356545
reference_title: A common mutation in the COG7 gene with a consistent phenotype including microcephaly, adducted thumbs, growth retardation, VSD and episodes of hyperthermia.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The siblings and an unrelated single child of consanguineous parents
presented with growth retardation, progressive, severe microcephaly,
hypotonia, adducted thumbs, feeding problems by gastrointestinal
pseudo-obstruction, failure to thrive, cardiac anomalies, wrinkled skin
and episodes of extreme hyperthermia.
explanation: >-
The clinical series directly reports progressive severe microcephaly.
- target: Hypotonia
description: Hypotonia is reported among characteristic neurologic findings.
causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
evidence:
- reference: PMID:17356545
reference_title: A common mutation in the COG7 gene with a consistent phenotype including microcephaly, adducted thumbs, growth retardation, VSD and episodes of hyperthermia.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The siblings and an unrelated single child of consanguineous parents
presented with growth retardation, progressive, severe microcephaly,
hypotonia, adducted thumbs, feeding problems by gastrointestinal
pseudo-obstruction, failure to thrive, cardiac anomalies, wrinkled skin
and episodes of extreme hyperthermia.
explanation: >-
The COG7 series directly reports hypotonia.
- target: Growth delay
description: Growth retardation is reported in affected COG7-CDG patients.
causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
evidence:
- reference: PMID:17356545
reference_title: A common mutation in the COG7 gene with a consistent phenotype including microcephaly, adducted thumbs, growth retardation, VSD and episodes of hyperthermia.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The siblings and an unrelated single child of consanguineous parents
presented with growth retardation, progressive, severe microcephaly,
hypotonia, adducted thumbs, feeding problems by gastrointestinal
pseudo-obstruction, failure to thrive, cardiac anomalies, wrinkled skin
and episodes of extreme hyperthermia.
explanation: >-
The clinical series directly reports growth retardation.
- target: Failure to thrive
description: Failure to thrive is reported in affected COG7-CDG patients.
causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
evidence:
- reference: PMID:17356545
reference_title: A common mutation in the COG7 gene with a consistent phenotype including microcephaly, adducted thumbs, growth retardation, VSD and episodes of hyperthermia.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The siblings and an unrelated single child of consanguineous parents
presented with growth retardation, progressive, severe microcephaly,
hypotonia, adducted thumbs, feeding problems by gastrointestinal
pseudo-obstruction, failure to thrive, cardiac anomalies, wrinkled skin
and episodes of extreme hyperthermia.
explanation: >-
The clinical series directly reports failure to thrive.
- name: Gastrointestinal dysmotility and feeding involvement
description: >-
COG7-CDG patients can have feeding problems caused by gastrointestinal
pseudo-obstruction.
evidence:
- reference: PMID:17356545
reference_title: A common mutation in the COG7 gene with a consistent phenotype including microcephaly, adducted thumbs, growth retardation, VSD and episodes of hyperthermia.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The siblings and an unrelated single child of consanguineous parents
presented with growth retardation, progressive, severe microcephaly,
hypotonia, adducted thumbs, feeding problems by gastrointestinal
pseudo-obstruction, failure to thrive, cardiac anomalies, wrinkled skin
and episodes of extreme hyperthermia.
explanation: >-
The clinical series reports feeding problems by gastrointestinal
pseudo-obstruction.
downstream:
- target: Feeding difficulties
description: Feeding problems are reported in COG7-CDG.
causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
evidence:
- reference: PMID:17356545
reference_title: A common mutation in the COG7 gene with a consistent phenotype including microcephaly, adducted thumbs, growth retardation, VSD and episodes of hyperthermia.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The siblings and an unrelated single child of consanguineous parents
presented with growth retardation, progressive, severe microcephaly,
hypotonia, adducted thumbs, feeding problems by gastrointestinal
pseudo-obstruction, failure to thrive, cardiac anomalies, wrinkled skin
and episodes of extreme hyperthermia.
explanation: >-
The clinical series directly reports feeding problems.
- target: Intestinal pseudo-obstruction
description: >-
Feeding problems are attributed to gastrointestinal pseudo-obstruction in
the reported COG7-CDG patients.
causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
evidence:
- reference: PMID:17356545
reference_title: A common mutation in the COG7 gene with a consistent phenotype including microcephaly, adducted thumbs, growth retardation, VSD and episodes of hyperthermia.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The siblings and an unrelated single child of consanguineous parents
presented with growth retardation, progressive, severe microcephaly,
hypotonia, adducted thumbs, feeding problems by gastrointestinal
pseudo-obstruction, failure to thrive, cardiac anomalies, wrinkled skin
and episodes of extreme hyperthermia.
explanation: >-
The COG7 series directly reports gastrointestinal pseudo-obstruction.
- name: Cardiac and thermoregulatory involvement
description: >-
COG7-CDG includes cardiac anomalies and episodes of extreme hyperthermia in
reported patients.
evidence:
- reference: PMID:17356545
reference_title: A common mutation in the COG7 gene with a consistent phenotype including microcephaly, adducted thumbs, growth retardation, VSD and episodes of hyperthermia.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The siblings and an unrelated single child of consanguineous parents
presented with growth retardation, progressive, severe microcephaly,
hypotonia, adducted thumbs, feeding problems by gastrointestinal
pseudo-obstruction, failure to thrive, cardiac anomalies, wrinkled skin
and episodes of extreme hyperthermia.
explanation: >-
The clinical series directly reports cardiac anomalies and episodes of
extreme hyperthermia.
downstream:
- target: Ventricular septal defect
description: >-
Ventricular septal defect is named in the paper title as a consistent
COG7-CDG phenotype.
causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
evidence:
- reference: PMID:17356545
reference_title: A common mutation in the COG7 gene with a consistent phenotype including microcephaly, adducted thumbs, growth retardation, VSD and episodes of hyperthermia.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
A common mutation in the COG7 gene with a consistent phenotype
including microcephaly, adducted thumbs, growth retardation, VSD and
episodes of hyperthermia.
explanation: >-
The title specifically names VSD as part of the consistent phenotype.
- target: Recurrent hyperthermia
description: Episodes of extreme hyperthermia are reported in COG7-CDG.
causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
evidence:
- reference: PMID:17356545
reference_title: A common mutation in the COG7 gene with a consistent phenotype including microcephaly, adducted thumbs, growth retardation, VSD and episodes of hyperthermia.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The siblings and an unrelated single child of consanguineous parents
presented with growth retardation, progressive, severe microcephaly,
hypotonia, adducted thumbs, feeding problems by gastrointestinal
pseudo-obstruction, failure to thrive, cardiac anomalies, wrinkled skin
and episodes of extreme hyperthermia.
explanation: >-
The clinical series directly reports episodes of extreme hyperthermia.
- name: Skin involvement
description: Wrinkled skin is reported among characteristic COG7-CDG findings.
evidence:
- reference: PMID:17356545
reference_title: A common mutation in the COG7 gene with a consistent phenotype including microcephaly, adducted thumbs, growth retardation, VSD and episodes of hyperthermia.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The siblings and an unrelated single child of consanguineous parents
presented with growth retardation, progressive, severe microcephaly,
hypotonia, adducted thumbs, feeding problems by gastrointestinal
pseudo-obstruction, failure to thrive, cardiac anomalies, wrinkled skin
and episodes of extreme hyperthermia.
explanation: The clinical series directly reports wrinkled skin.
downstream:
- target: Cutis laxa
description: >-
Wrinkled skin is represented using the HPO cutis laxa term, whose
definition includes wrinkled skin.
causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
evidence:
- reference: PMID:17356545
reference_title: A common mutation in the COG7 gene with a consistent phenotype including microcephaly, adducted thumbs, growth retardation, VSD and episodes of hyperthermia.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The siblings and an unrelated single child of consanguineous parents
presented with growth retardation, progressive, severe microcephaly,
hypotonia, adducted thumbs, feeding problems by gastrointestinal
pseudo-obstruction, failure to thrive, cardiac anomalies, wrinkled skin
and episodes of extreme hyperthermia.
explanation: >-
The COG7 series directly reports wrinkled skin; HP:0000973 is the
closest HPO match because its definition includes wrinkled skin.
- name: Congenital limb involvement
description: Adducted thumbs are reported as part of the COG7-CDG phenotype.
evidence:
- reference: PMID:17356545
reference_title: A common mutation in the COG7 gene with a consistent phenotype including microcephaly, adducted thumbs, growth retardation, VSD and episodes of hyperthermia.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The siblings and an unrelated single child of consanguineous parents
presented with growth retardation, progressive, severe microcephaly,
hypotonia, adducted thumbs, feeding problems by gastrointestinal
pseudo-obstruction, failure to thrive, cardiac anomalies, wrinkled skin
and episodes of extreme hyperthermia.
explanation: The clinical series directly reports adducted thumbs.
downstream:
- target: Adducted thumb
description: Adducted thumbs are reported in COG7-CDG.
causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
evidence:
- reference: PMID:17356545
reference_title: A common mutation in the COG7 gene with a consistent phenotype including microcephaly, adducted thumbs, growth retardation, VSD and episodes of hyperthermia.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The siblings and an unrelated single child of consanguineous parents
presented with growth retardation, progressive, severe microcephaly,
hypotonia, adducted thumbs, feeding problems by gastrointestinal
pseudo-obstruction, failure to thrive, cardiac anomalies, wrinkled skin
and episodes of extreme hyperthermia.
explanation: The clinical series directly reports adducted thumbs.
phenotypes:
- name: Abnormal Glycosylation
category: Biochemical
description: >-
Serum transferrin isoelectric focusing and apolipoprotein C-III
isoelectric focusing show abnormal N-linked and O-linked glycosylation.
phenotype_term:
preferred_term: Abnormal glycosylation
term:
id: HP:0012345
label: Abnormal glycosylation
evidence:
- reference: PMID:16151902
reference_title: Clinical and biochemical presentation of siblings with COG-7 deficiency, a lethal multiple O- and N-glycosylation disorder.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Isoelectric focusing of serum sialotransferrins showed a type 2-like CDG pattern."
explanation: >-
Serum transferrin IEF directly supports abnormal N-glycosylation.
- reference: PMID:16151902
reference_title: Clinical and biochemical presentation of siblings with COG-7 deficiency, a lethal multiple O- and N-glycosylation disorder.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "O-Glycosylation was investigated by isoelectric focusing of apolipoprotein C-III, which showed increased fractions of hyposialylated isoforms."
explanation: >-
Apolipoprotein C-III IEF directly supports abnormal O-glycosylation.
- name: Abnormal facial shape
category: Clinical
description: >-
Dysmorphic appearance was reported in the original affected siblings with
severe infantile COG7-CDG; no more specific facial gestalt is available in
the cached abstract.
phenotype_term:
preferred_term: Abnormal facial shape
term:
id: HP:0001999
label: Abnormal facial shape
evidence:
- reference: PMID:16151902
reference_title: Clinical and biochemical presentation of siblings with COG-7 deficiency, a lethal multiple O- and N-glycosylation disorder.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "We report on two dysmorphic siblings with severe liver disease who died at the age of a few weeks."
explanation: >-
The clinical and biochemical report explicitly describes affected
siblings as dysmorphic, which is modeled with the broad HPO facial-shape
term because the abstract does not provide a more specific gestalt.
- name: Progressive microcephaly
category: Neurological
description: >-
Progressive severe microcephaly is part of the recurrent COG7-CDG clinical
presentation.
phenotype_term:
preferred_term: Progressive severe microcephaly
term:
id: HP:0000252
label: Microcephaly
clinical_course: PROGRESSIVE
severity: SEVERE
evidence:
- reference: PMID:17356545
reference_title: A common mutation in the COG7 gene with a consistent phenotype including microcephaly, adducted thumbs, growth retardation, VSD and episodes of hyperthermia.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The siblings and an unrelated single child of consanguineous parents
presented with growth retardation, progressive, severe microcephaly,
hypotonia, adducted thumbs, feeding problems by gastrointestinal
pseudo-obstruction, failure to thrive, cardiac anomalies, wrinkled skin
and episodes of extreme hyperthermia.
explanation: >-
The clinical series directly reports progressive severe microcephaly in
affected COG7-CDG patients.
- name: Hypotonia
category: Neurological
description: Hypotonia is reported among characteristic COG7-CDG findings.
phenotype_term:
preferred_term: Hypotonia
term:
id: HP:0001252
label: Hypotonia
evidence:
- reference: PMID:17356545
reference_title: A common mutation in the COG7 gene with a consistent phenotype including microcephaly, adducted thumbs, growth retardation, VSD and episodes of hyperthermia.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The siblings and an unrelated single child of consanguineous parents
presented with growth retardation, progressive, severe microcephaly,
hypotonia, adducted thumbs, feeding problems by gastrointestinal
pseudo-obstruction, failure to thrive, cardiac anomalies, wrinkled skin
and episodes of extreme hyperthermia.
explanation: The clinical series directly reports hypotonia.
- name: Growth delay
category: Growth
description: Growth retardation is reported in COG7-CDG patients.
phenotype_term:
preferred_term: Growth retardation
term:
id: HP:0001510
label: Growth delay
evidence:
- reference: PMID:17356545
reference_title: A common mutation in the COG7 gene with a consistent phenotype including microcephaly, adducted thumbs, growth retardation, VSD and episodes of hyperthermia.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The siblings and an unrelated single child of consanguineous parents
presented with growth retardation, progressive, severe microcephaly,
hypotonia, adducted thumbs, feeding problems by gastrointestinal
pseudo-obstruction, failure to thrive, cardiac anomalies, wrinkled skin
and episodes of extreme hyperthermia.
explanation: The clinical series directly reports growth retardation.
- name: Failure to thrive
category: Growth
description: Failure to thrive is reported in affected COG7-CDG patients.
phenotype_term:
preferred_term: Failure to thrive
term:
id: HP:0001508
label: Failure to thrive
evidence:
- reference: PMID:17356545
reference_title: A common mutation in the COG7 gene with a consistent phenotype including microcephaly, adducted thumbs, growth retardation, VSD and episodes of hyperthermia.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The siblings and an unrelated single child of consanguineous parents
presented with growth retardation, progressive, severe microcephaly,
hypotonia, adducted thumbs, feeding problems by gastrointestinal
pseudo-obstruction, failure to thrive, cardiac anomalies, wrinkled skin
and episodes of extreme hyperthermia.
explanation: The clinical series directly reports failure to thrive.
- name: Feeding difficulties
category: Gastrointestinal
description: >-
Feeding problems are reported in COG7-CDG and were attributed to
gastrointestinal pseudo-obstruction in the clinical series.
phenotype_term:
preferred_term: Feeding difficulties
term:
id: HP:0011968
label: Feeding difficulties
evidence:
- reference: PMID:17356545
reference_title: A common mutation in the COG7 gene with a consistent phenotype including microcephaly, adducted thumbs, growth retardation, VSD and episodes of hyperthermia.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The siblings and an unrelated single child of consanguineous parents
presented with growth retardation, progressive, severe microcephaly,
hypotonia, adducted thumbs, feeding problems by gastrointestinal
pseudo-obstruction, failure to thrive, cardiac anomalies, wrinkled skin
and episodes of extreme hyperthermia.
explanation: The clinical series directly reports feeding problems.
- name: Intestinal pseudo-obstruction
category: Gastrointestinal
description: >-
Gastrointestinal pseudo-obstruction is reported as the cause of feeding
problems in affected COG7-CDG patients.
phenotype_term:
preferred_term: Gastrointestinal pseudo-obstruction
term:
id: HP:0004389
label: Intestinal pseudo-obstruction
evidence:
- reference: PMID:17356545
reference_title: A common mutation in the COG7 gene with a consistent phenotype including microcephaly, adducted thumbs, growth retardation, VSD and episodes of hyperthermia.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The siblings and an unrelated single child of consanguineous parents
presented with growth retardation, progressive, severe microcephaly,
hypotonia, adducted thumbs, feeding problems by gastrointestinal
pseudo-obstruction, failure to thrive, cardiac anomalies, wrinkled skin
and episodes of extreme hyperthermia.
explanation: >-
The clinical series directly reports feeding problems by gastrointestinal
pseudo-obstruction.
- name: Ventricular septal defect
category: Cardiac
description: >-
Ventricular septal defect is named as part of the consistent COG7-CDG
phenotype.
phenotype_term:
preferred_term: Ventricular septal defect
term:
id: HP:0001629
label: Ventricular septal defect
evidence:
- reference: PMID:17356545
reference_title: A common mutation in the COG7 gene with a consistent phenotype including microcephaly, adducted thumbs, growth retardation, VSD and episodes of hyperthermia.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
A common mutation in the COG7 gene with a consistent phenotype including
microcephaly, adducted thumbs, growth retardation, VSD and episodes of
hyperthermia.
explanation: >-
The paper title specifically names VSD as part of the consistent
phenotype; the abstract body also reports cardiac anomalies.
- name: Recurrent hyperthermia
category: Clinical
description: Episodes of extreme hyperthermia are reported in COG7-CDG.
phenotype_term:
preferred_term: Episodes of extreme hyperthermia
term:
id: HP:0001945
label: Fever
temporality: RECURRENT
evidence:
- reference: PMID:17356545
reference_title: A common mutation in the COG7 gene with a consistent phenotype including microcephaly, adducted thumbs, growth retardation, VSD and episodes of hyperthermia.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The siblings and an unrelated single child of consanguineous parents
presented with growth retardation, progressive, severe microcephaly,
hypotonia, adducted thumbs, feeding problems by gastrointestinal
pseudo-obstruction, failure to thrive, cardiac anomalies, wrinkled skin
and episodes of extreme hyperthermia.
explanation: The clinical series directly reports episodes of extreme hyperthermia.
- name: Cutis laxa
category: Dermatologic
description: >-
Wrinkled skin is reported in COG7-CDG and is represented with the HPO cutis
laxa term because its definition includes wrinkled skin.
phenotype_term:
preferred_term: Wrinkled skin
term:
id: HP:0000973
label: Cutis laxa
evidence:
- reference: PMID:17356545
reference_title: A common mutation in the COG7 gene with a consistent phenotype including microcephaly, adducted thumbs, growth retardation, VSD and episodes of hyperthermia.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The siblings and an unrelated single child of consanguineous parents
presented with growth retardation, progressive, severe microcephaly,
hypotonia, adducted thumbs, feeding problems by gastrointestinal
pseudo-obstruction, failure to thrive, cardiac anomalies, wrinkled skin
and episodes of extreme hyperthermia.
explanation: >-
The COG7 clinical series reports wrinkled skin; HP:0000973 is used as
the closest HPO term because its definition includes wrinkled skin.
- name: Adducted thumb
category: Musculoskeletal
description: Adducted thumbs are reported in affected COG7-CDG patients.
phenotype_term:
preferred_term: Adducted thumb
term:
id: HP:0001181
label: Adducted thumb
evidence:
- reference: PMID:17356545
reference_title: A common mutation in the COG7 gene with a consistent phenotype including microcephaly, adducted thumbs, growth retardation, VSD and episodes of hyperthermia.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The siblings and an unrelated single child of consanguineous parents
presented with growth retardation, progressive, severe microcephaly,
hypotonia, adducted thumbs, feeding problems by gastrointestinal
pseudo-obstruction, failure to thrive, cardiac anomalies, wrinkled skin
and episodes of extreme hyperthermia.
explanation: The clinical series directly reports adducted thumbs.
- name: Severe Liver Disease
category: Hepatic
description: >-
Severe infantile liver disease was reported in the original clinical and
biochemical description of COG7 deficiency.
phenotype_term:
preferred_term: Abnormality of the liver
term:
id: HP:0001392
label: Abnormality of the liver
evidence:
- reference: PMID:16151902
reference_title: Clinical and biochemical presentation of siblings with COG-7 deficiency, a lethal multiple O- and N-glycosylation disorder.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
We report on two dysmorphic siblings with severe liver disease who died
at the age of a few weeks.
explanation: >-
This directly supports severe liver disease and early lethality in
affected siblings.
sequelae:
- target: Fatal Infantile Course
description: >-
Severe liver disease in the reported affected siblings was associated
with death within the first weeks of life.
causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
evidence:
- reference: PMID:16151902
reference_title: Clinical and biochemical presentation of siblings with COG-7 deficiency, a lethal multiple O- and N-glycosylation disorder.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
We report on two dysmorphic siblings with severe liver disease who died
at the age of a few weeks.
explanation: >-
The same sibling report links severe liver disease with death during
early infancy.
- name: Fatal Infantile Course
category: Clinical
description: >-
The earliest reported affected siblings died within the first weeks of life.
evidence:
- reference: PMID:16151902
reference_title: Clinical and biochemical presentation of siblings with COG-7 deficiency, a lethal multiple O- and N-glycosylation disorder.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
We report on two dysmorphic siblings with severe liver disease who died
at the age of a few weeks.
explanation: >-
The sibling report supports an early fatal clinical course in severe
COG7-CDG.
genetic:
- name: COG7 pathogenic variants
association: Causal
relationship_type: CAUSATIVE
presence: Pathogenic
gene_term:
preferred_term: COG7
term:
id: hgnc:18622
label: COG7
evidence:
- reference: PMID:15107842
reference_title: Mutation of the COG complex subunit gene COG7 causes a lethal congenital disorder.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Here we describe two siblings with a fatal form of CDG caused by a
mutation in the gene encoding COG-7, a subunit of the conserved
oligomeric Golgi (COG) complex.
explanation: >-
This establishes COG7 as the causal gene for the disorder.
biochemical:
- name: Type II-like serum transferrin isoelectric focusing pattern
presence: ABNORMAL
context: >-
Type II-like transferrin IEF reflects abnormal Golgi-stage N-glycan
processing.
readouts:
- target: Combined N- and O-glycosylation Defect
relationship: READOUT_OF
direction: POSITIVE
endpoint_context: DIAGNOSTIC
interpretation: >-
A type II-like serum sialotransferrin pattern reports the N-glycan
processing component of the combined Golgi glycosylation defect.
evidence:
- reference: PMID:16151902
reference_title: Clinical and biochemical presentation of siblings with COG-7 deficiency, a lethal multiple O- and N-glycosylation disorder.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Isoelectric focusing of serum sialotransferrins showed a type 2-like
CDG pattern.
explanation: >-
Serum sialotransferrin isoelectric focusing directly demonstrates the
type II-like glycosylation abnormality.
evidence:
- reference: PMID:16151902
reference_title: Clinical and biochemical presentation of siblings with COG-7 deficiency, a lethal multiple O- and N-glycosylation disorder.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Isoelectric focusing of serum sialotransferrins showed a type 2-like CDG
pattern.
explanation: >-
This directly supports the diagnostic transferrin IEF abnormality.
- name: Hyposialylated apolipoprotein C-III isoforms
presence: INCREASED
context: >-
Apolipoprotein C-III IEF can reveal O-glycosylation defects in COG7-CDG.
readouts:
- target: Combined N- and O-glycosylation Defect
relationship: READOUT_OF
direction: POSITIVE
endpoint_context: DIAGNOSTIC
interpretation: >-
Increased hyposialylated apolipoprotein C-III isoforms report the
O-glycosylation component of the combined Golgi glycosylation defect.
evidence:
- reference: PMID:16151902
reference_title: Clinical and biochemical presentation of siblings with COG-7 deficiency, a lethal multiple O- and N-glycosylation disorder.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
O-Glycosylation was investigated by isoelectric focusing of
apolipoprotein C-III, which showed increased fractions of
hyposialylated isoforms.
explanation: >-
Apolipoprotein C-III isoelectric focusing directly reports abnormal
O-glycosylation.
evidence:
- reference: PMID:16151902
reference_title: Clinical and biochemical presentation of siblings with COG-7 deficiency, a lethal multiple O- and N-glycosylation disorder.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
O-Glycosylation was investigated by isoelectric focusing of apolipoprotein
C-III, which showed increased fractions of hyposialylated isoforms.
explanation: >-
This directly supports abnormal apolipoprotein C-III isoforms as an
O-glycosylation biomarker.
- name: Increased plasma lysosomal enzyme activities
presence: INCREASED
context: >-
Elevated lysosomal enzyme activities in plasma are a reported biochemical
abnormality in the original COG7-CDG siblings.
readouts:
- target: Combined N- and O-glycosylation Defect
relationship: READOUT_OF
direction: POSITIVE
endpoint_context: DIAGNOSTIC
interpretation: >-
Increased plasma lysosomal enzyme activities are a reported accompanying
biochemical abnormality of the multiple Golgi glycosylation defect.
evidence:
- reference: PMID:16151902
reference_title: Clinical and biochemical presentation of siblings with COG-7 deficiency, a lethal multiple O- and N-glycosylation disorder.
supports: PARTIAL
evidence_source: HUMAN_CLINICAL
snippet: "Increased activities of lysosomal enzymes in plasma were found"
explanation: >-
The abnormality is reported in COG7-CDG siblings with the multiple
Golgi glycosylation defect, but the abstract does not define the exact
mechanistic intermediate.
evidence:
- reference: PMID:16151902
reference_title: Clinical and biochemical presentation of siblings with COG-7 deficiency, a lethal multiple O- and N-glycosylation disorder.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Increased activities of lysosomal enzymes in plasma were found"
explanation: >-
The abstract directly reports increased plasma lysosomal enzyme activities.
- name: Decreased total plasma sialic acid
biomarker_term:
preferred_term: sialic acid
term:
id: CHEBI:26667
label: sialic acid
presence: DECREASED
context: >-
Reduced total sialic acid in plasma is a directly reported biochemical
abnormality in COG7-CDG.
readouts:
- target: Combined N- and O-glycosylation Defect
relationship: READOUT_OF
direction: NEGATIVE
endpoint_context: DIAGNOSTIC
interpretation: >-
Decreased total plasma sialic acid reports defective glycoprotein
sialylation in the combined Golgi glycosylation defect.
evidence:
- reference: PMID:16151902
reference_title: Clinical and biochemical presentation of siblings with COG-7 deficiency, a lethal multiple O- and N-glycosylation disorder.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "total sialic acid in plasma was strongly decreased"
explanation: >-
Markedly decreased total plasma sialic acid is a direct biochemical
readout of the reported COG7-CDG glycosylation disturbance.
evidence:
- reference: PMID:16151902
reference_title: Clinical and biochemical presentation of siblings with COG-7 deficiency, a lethal multiple O- and N-glycosylation disorder.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "total sialic acid in plasma was strongly decreased"
explanation: >-
The abstract directly reports markedly decreased total plasma sialic acid.
diagnosis:
- name: Serum transferrin and apolipoprotein C-III isoelectric focusing
description: >-
A type II-like serum sialotransferrin pattern and hyposialylated
apolipoprotein C-III isoforms support a combined N- and O-glycosylation
defect.
results: Type II-like transferrin IEF with hyposialylated apolipoprotein C-III isoforms supports COG7-CDG evaluation.
evidence:
- reference: PMID:16151902
reference_title: Clinical and biochemical presentation of siblings with COG-7 deficiency, a lethal multiple O- and N-glycosylation disorder.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
This report on patients with a new variant of CDG, due to a multiple
Golgi defect, emphasizes in addition to sialotransferrins the importance
of analysis of a serum O-linked glycoprotein, e.g. apolipoprotein C-III,
in unclassified CDG-X cases.
explanation: >-
The abstract recommends adding O-linked glycoprotein analysis to
sialotransferrin testing for unclassified CDG cases.
- name: Molecular testing for COG7
diagnosis_term:
preferred_term: genetic testing
term:
id: MAXO:0000127
label: genetic testing
description: >-
Sequencing or targeted molecular testing can confirm pathogenic COG7
variants in a compatible CDG-II biochemical and clinical presentation.
results: Biallelic pathogenic COG7 variants confirm the molecular diagnosis.
evidence:
- reference: PMID:15107842
reference_title: Mutation of the COG complex subunit gene COG7 causes a lethal congenital disorder.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Here we describe two siblings with a fatal form of CDG caused by a
mutation in the gene encoding COG-7, a subunit of the conserved
oligomeric Golgi (COG) complex.
explanation: >-
Molecular identification of the COG7 mutation supports genetic testing as
diagnostic confirmation.
treatments:
- name: Supportive and symptomatic care
description: >-
No COG7-specific disease-modifying treatment is established; current care is
supportive and directed to organ complications, while CDG-wide therapeutic
discovery remains an unmet need.
treatment_term:
preferred_term: supportive care
term:
id: MAXO:0000950
label: supportive care
evidence:
- reference: PMID:37858231
reference_title: "Congenital disorders of glycosylation (CDG): state of the art in 2022."
supports: PARTIAL
evidence_source: OTHER
snippet: >-
However, much remains to be understood, with targeted therapies'
discovery and approval being the most urgent unmet need.
explanation: >-
This supports the absence of established targeted CDG therapies, making
supportive care the conservative modeled management category.
clinical_trials:
- name: NCT04199000
status: RECRUITING
description: >-
CDG-wide observational natural-history study that may include genetically
confirmed rare CDG subtypes such as COG7-CDG.
evidence:
- reference: clinicaltrials:NCT04199000
reference_title: Clinical and Basic Investigations Into Congenital Disorders of Glycosylation
supports: PARTIAL
evidence_source: HUMAN_CLINICAL
snippet: >-
The purpose of this research is to study the natural history of
congenital disorders of glycosylation and its causes and treatments.
explanation: >-
The trial is CDG-wide rather than COG7-specific, so it partially supports
relevance to COG7-CDG.
notes: >-
Falcon deep research completed on 2026-05-09. The YAML intentionally uses
only claims with PMID or ClinicalTrials.gov cache-backed snippets. Broader
report findings on seizures, infections, cardiac insufficiency, founder
effects, and endocrine findings were not modeled unless supported by fetched
abstract text.
datasets: []
Name: COG7-congenital disorder of glycosylation (COG7-CDG) (spaapen2005clinicalandbiochemical pages 3-6, francisco2023congenitaldisordersof pages 4-6)
Category: Mendelian (autosomal recessive) (wu2004mutationofthe pages 3-4, zeevaert2008deficienciesinsubunits pages 2-3)
Known identifier in retrieved sources: MIM/OMIM 608779 (unsal2026endocrineimplicationsof pages 15-16, francisco2023congenitaldisordersof pages 4-6)
MONDO ID: Not identified in retrieved sources (no MONDO cross-reference present in the documents retrieved for this run).
COG7-CDG is a severe, typically neonatal-onset congenital disorder of glycosylation caused by loss of function of COG7, a subunit of the conserved oligomeric Golgi (COG) complex, leading to impaired Golgi trafficking and combined N- and O-glycosylation defects (wu2004mutationofthe pages 2-3, francisco2023congenitaldisordersof pages 2-4).
Not found in retrieved texts for this run: Orphanet number, ICD-10/ICD-11 code, MeSH disease heading, MONDO ID.
Most disease-specific information available here is aggregated from published case reports/series and reviews, rather than EHR-derived cohorts (e.g., index families and a 6-patient founder series) (wu2004mutationofthe pages 1-2, zeevaert2008deficienciesinsubunits pages 3-5).
Primary cause: biallelic pathogenic variants in COG7 impair COG complex integrity and Golgi trafficking, producing broad glycosylation abnormalities (wu2004mutationofthe pages 2-3, wu2004mutationofthe pages 3-4).
Inheritance: autosomal recessive; multiple affected families are consanguineous and show homozygosity for the recurrent splice variant (wu2004mutationofthe pages 3-4, zeevaert2008deficienciesinsubunits pages 3-5).
No genetic or environmental protective factors were identified in retrieved sources.
COG7-CDG is classically a rapidly progressive neonatal multisystem disorder with early lethality (weeks to months) (wu2004mutationofthe pages 1-2, zeevaert2008deficienciesinsubunits pages 3-5).
Case reports and a North African founder series describe a consistent phenotype including: * Growth impairment / prenatal growth retardation (HPO suggestion: HP:0001511 Intrauterine growth restriction) (wu2004mutationofthe pages 1-2, zeevaert2008deficienciesinsubunits pages 3-5) * Progressive microcephaly (HP:0000252 Microcephaly) (unsal2026endocrineimplicationsof pages 15-16, zeevaert2008deficienciesinsubunits pages 3-5) * Dysmorphic features (e.g., micrognathia; low-set/dysplastic ears; loose/wrinkled skin reported) (HP:0000347 Micrognathia; HP:0000369 Low-set ears; HP:0000974 Hyperelastic skin / cutis laxa-like features) (wu2004mutationofthe pages 1-2, zeevaert2008deficienciesinsubunits pages 3-5) * Generalized hypotonia (HP:0001252 Hypotonia) (wu2004mutationofthe pages 1-2, zeevaert2008deficienciesinsubunits pages 3-5) * Severe encephalopathy / seizures / epilepsy (HP:0001298 Encephalopathy; HP:0001250 Seizures) (wu2004mutationofthe pages 1-2, zeevaert2008deficienciesinsubunits pages 3-5) * Cholestatic liver disease / hepatopathy (HP:0001396 Cholestasis; HP:0001402 Hepatomegaly) (spaapen2005clinicalandbiochemical pages 3-6, zeevaert2008deficienciesinsubunits pages 3-5) * Recurrent infections (HP:0002719 Recurrent infections) (wu2004mutationofthe pages 1-2) * Cardiac defects including ASD/VSD (HP:0001631 Atrial septal defect; HP:0001629 Ventricular septal defect) (zeevaert2008deficienciesinsubunits pages 3-5) * Episodes of hyperthermia (HP:0001945 Fever / hyperthermia episodes) (zeevaert2008deficienciesinsubunits pages 3-5) * Hand anomalies including adducted thumbs/overlapping fingers/ulnar deviation/contractures (HP:0001184 Adducted thumbs; HP:0009484 Ulnar deviation of the hand) (unsal2026endocrineimplicationsof pages 15-16)
Direct QoL instrument results specific to COG7-CDG were not found; however, the reported severe neonatal encephalopathy, cholestatic liver disease, seizures, and early death imply profound impairment (wu2004mutationofthe pages 1-2, zeevaert2008deficienciesinsubunits pages 3-5).
A recurrent homozygous splice variant is prominent: * IVS1+4A>C (also reported as c.169+4A>C) → aberrant splicing with a 19-bp deletion in mRNA and marked reduction/absence of COG7 protein (wu2004mutationofthe pages 2-3, zeevaert2008deficienciesinsubunits pages 3-5).
Functional consequence: loss of COG7 destabilizes the COG complex, disrupts Golgi trafficking, reduces nucleotide-sugar transport into the Golgi, and reduces glycosyltransferase activities, producing combined N- and O-glycosylation defects (wu2004mutationofthe pages 2-3, wu2004mutationofthe pages 4-6).
No modifier genes, epigenetic mechanisms, or chromosomal abnormalities specific to COG7-CDG were identified in retrieved sources.
COG7-CDG is a monogenic disorder; non-genetic environmental contributors or infectious triggers were not reported in the retrieved evidence.
GO Biological Process (examples): * Golgi organization; vesicle tethering / retrograde vesicle-mediated transport, Golgi to ER; protein glycosylation; protein sialylation (mechanistically implied by trafficking and sialylation defects) (wu2004mutationofthe pages 2-3, francisco2023congenitaldisordersof pages 2-4).
Cell types (CL, examples):
* Fibroblast (patient-derived dermal fibroblasts are the key experimental system) (wu2004mutationofthe pages 2-3, spaapen2005clinicalandbiochemical pages 1-3).
* Hepatocyte; neuron (inferred from dominant liver and CNS involvement described clinically; direct cellular profiling not found) (zeevaert2008deficienciesinsubunits pages 3-5, francisco2023congenitaldisordersof pages 1-2).
Based on multisystem involvement reported: * Brain/CNS (encephalopathy, seizures; cerebral/cerebellar atrophy described in summaries) (UBERON examples: UBERON:0000955 brain; UBERON:0002037 cerebellum) (unsal2026endocrineimplicationsof pages 15-16, zeevaert2008deficienciesinsubunits pages 3-5). * Liver (cholestasis, elevated transaminases, hepatopathy) (UBERON:0002107 liver) (spaapen2005clinicalandbiochemical pages 3-6, zeevaert2008deficienciesinsubunits pages 3-5). * Heart (ASD/VSD; cardiac insufficiency) (UBERON:0000948 heart) (wu2004mutationofthe pages 1-2, zeevaert2008deficienciesinsubunits pages 3-5). * Immune/host defense (recurrent infections) (wu2004mutationofthe pages 1-2).
Subcellular localization central to pathogenesis: Golgi apparatus (GO cellular component: Golgi apparatus) (wu2004mutationofthe pages 2-3).
Autosomal recessive, frequently in consanguineous families (zeevaert2008deficienciesinsubunits pages 2-3, zeevaert2008deficienciesinsubunits pages 3-5).
Population prevalence/incidence estimates were not identified in retrieved evidence.
A cohort described 6 patients (2 Tunisia, 4 Morocco) all homozygous for IVS1+4A>C / c.169+4A>C, and haplotyping suggested a shared ancestral haplotype consistent with a founder effect in North Africa (zeevaert2008deficienciesinsubunits pages 3-5).
Deaths were reported between 5 weeks and 9 months in the 6-patient series (zeevaert2008deficienciesinsubunits pages 3-5); the index sibling pair died at 5 and 10 weeks (wu2004mutationofthe pages 1-2).
1) Serum transferrin isoforms (IEF)
* Abnormal type II / type 2-like CDG pattern is a key screening biomarker for processing/trafficking CDGs (wu2004mutationofthe pages 1-2, spaapen2005clinicalandbiochemical pages 3-6).
* Visual evidence: transferrin IEF patterns from affected siblings are shown in Spaapen et al. 2005 (spaapen2005clinicalandbiochemical media a32196a0, spaapen2005clinicalandbiochemical media 9596aac9).
2) Apolipoprotein C-III isoforms (IEF)
* ApoC-III IEF demonstrates O-glycan hyposialylation, supporting combined N- and O-glycosylation involvement (spaapen2005clinicalandbiochemical pages 3-6).
* Visual evidence: apoC-III IEF figure in Spaapen et al. 2005 (spaapen2005clinicalandbiochemical media a32196a0, spaapen2005clinicalandbiochemical media 9596aac9).
3) Sialic acid quantitation (blood/urine) * Low total plasma sialic acid reported in affected siblings (e.g., 321 and 599 µmol/L vs reference range) and increased urinary free sialic acid in one patient (spaapen2005clinicalandbiochemical pages 3-6).
4) Supportive labs * Elevated transaminases (200–890 U/L in the 6-patient series) and elevated CK in 4/6 (zeevaert2008deficienciesinsubunits pages 3-5).
Disease confirmation is via molecular detection of biallelic COG7 pathogenic variants (e.g., IVS1+4A>C) (wu2004mutationofthe pages 2-3, spaapen2005clinicalandbiochemical pages 3-6).
A 2023 state-of-the-art review highlights that while transferrin IEF historically underpinned CDG screening, genomic sequencing (WES/WGS) is now “very powerful” and may be the only route when biochemical biomarkers are absent (francisco2023congenitaldisordersof pages 4-6). The same review notes expanding glycomics biomarkers (e.g., ESI-QTOF-MS glycan profiling; additional glycoprotein biomarkers) (francisco2023congenitaldisordersof pages 4-6).
Not systematically enumerated in retrieved texts; however, differential diagnosis typically includes other Golgi/trafficking CDG and other causes of neonatal cholestasis/encephalopathy with abnormal transferrin IEF (supported generally by the CDG classification context) (francisco2023congenitaldisordersof pages 2-4, paprocka2021congenitaldisordersof pages 2-4).
COG7-CDG is most often lethal in early infancy in the classic phenotype, with fatality occurring as early as 5–10 weeks in initial siblings and by 9 months in the founder series (wu2004mutationofthe pages 1-2, zeevaert2008deficienciesinsubunits pages 3-5).
Prognostic biomarkers specific to COG7-CDG were not identified; severity is largely defined clinically and by multi-organ involvement (zeevaert2008deficienciesinsubunits pages 3-5).
No COG7-CDG-specific disease-modifying therapy was identified in the retrieved evidence.
A 2023 Orphanet Journal of Rare Diseases review states the urgency of developing targeted therapies and indicates that CDG patients often require ongoing management for multi-organ complications (francisco2023congenitaldisordersof pages 1-2). The review also states CDG treatment remains almost entirely symptomatic/supportive, with mannose supplementation for MPI-CDG as a key established exception (francisco2023congenitaldisordersof pages 2-4).
Given the presentation, standard practice typically includes: * seizure management (anti-seizure medications) (general CDG neurology management context) (paprocka2021congenitaldisordersof pages 2-4) * nutritional support / failure-to-thrive management * management of cholestasis and hepatic dysfunction * infection prevention and treatment * cardiology management for structural defects/heart failure These are consistent with the reported multi-organ involvement and severe neonatal course, though explicit COG7-CDG management protocols were not found in retrieved sources (wu2004mutationofthe pages 1-2, zeevaert2008deficienciesinsubunits pages 3-5).
Primary prevention is not applicable in the usual sense for a recessive Mendelian disorder; the principal prevention strategies are genetic counseling and carrier/prenatal testing in at-risk families (implied by AR inheritance and founder effect) (zeevaert2008deficienciesinsubunits pages 3-5).
No naturally occurring veterinary disease analogs specifically tied to COG7 were identified in retrieved sources.
Patient-derived dermal fibroblasts are the principal model system; mechanistic assays include: * trafficking assays (ST-GFP fluorescence recovery/photobleaching approaches) * nucleotide-sugar transport assays into Golgi * glycosyltransferase activity assays * lectin binding/neuraminidase treatment Importantly, complementation with wild-type COG7 cDNA rescues trafficking and glycosylation defects, supporting causality (wu2004mutationofthe pages 2-3, wu2004mutationofthe pages 4-6).
COG biology and phenotypes are also studied in CHO cell mutants (ldlB/ldlC), yeast, and animal models including Drosophila and C. elegans (general COG modeling context) (zeevaert2008deficienciesinsubunits pages 2-3).
A 2023 “state of the art” review highlights rapid progress driven by multi-omics and expanding gene discovery, and explicitly notes the unmet need for targeted therapies: “targeted therapies’ discovery and approval being the most urgent unmet need.” (published Oct 2023; URL: https://doi.org/10.1186/s13023-023-02879-z) (francisco2023congenitaldisordersof pages 1-2). The same review reports substantial expansion of known CDG genes/phenotypes (163 genes; 193 phenotypes) and emphasizes genomic sequencing as a key diagnostic route (francisco2023congenitaldisordersof pages 1-2, francisco2023congenitaldisordersof pages 4-6).
For trafficking-related CDG classification, the review places vesicular transport defects (including COG defects) within an “other (including multiple)” category (francisco2023congenitaldisordersof pages 2-4).
| Category | Structured fact | Evidence / key references |
|---|---|---|
| Disease name / synonyms | COG7-congenital disorder of glycosylation (COG7-CDG); older nomenclature includes CDG type IIe / CDG-IIe and COG-7 deficiency (spaapen2005clinicalandbiochemical pages 3-6) | Spaapen et al., 2005, J Inherit Metab Dis, DOI: https://doi.org/10.1007/s10545-005-0015-z (spaapen2005clinicalandbiochemical pages 3-6) |
| Identifier(s) | MIM/OMIM: 608779 reported for COG7-CDG in recent review tables (unsal2026endocrineimplicationsof pages 15-16, francisco2023congenitaldisordersof pages 4-6) | Ünsal & Özön, 2026, DOI: https://doi.org/10.4274/jcrpe.galenos.2025.2024-10-7; Francisco et al., 2023, DOI: https://doi.org/10.1186/s13023-023-02879-z (unsal2026endocrineimplicationsof pages 15-16, francisco2023congenitaldisordersof pages 4-6) |
| Disease class | Trafficking-related / Golgi homeostasis CDG affecting combined N- and O-glycosylation through COG complex dysfunction (wu2004mutationofthe pages 2-3, francisco2023congenitaldisordersof pages 2-4) | Wu et al., 2004, Nat Med, DOI: https://doi.org/10.1038/nm1041; Francisco et al., 2023, DOI: https://doi.org/10.1186/s13023-023-02879-z (wu2004mutationofthe pages 2-3, francisco2023congenitaldisordersof pages 2-4) |
| Inheritance | Autosomal recessive; reported in affected siblings and multiple consanguineous families (wu2004mutationofthe pages 3-4, zeevaert2008deficienciesinsubunits pages 2-3) | Wu et al., 2004, DOI: https://doi.org/10.1038/nm1041; Zeevaert et al., 2008, DOI: https://doi.org/10.1016/j.ymgme.2007.08.118 (wu2004mutationofthe pages 3-4, zeevaert2008deficienciesinsubunits pages 2-3) |
| Key pathogenic variant | Recurrent homozygous splice variant IVS1+4A>C, also reported as c.169+4A>C, causing aberrant splicing with a 19-bp deletion in mRNA and marked reduction/absence of COG7 protein (wu2004mutationofthe pages 2-3, spaapen2005clinicalandbiochemical pages 3-6, zeevaert2008deficienciesinsubunits pages 3-5) | Wu et al., 2004, DOI: https://doi.org/10.1038/nm1041; Spaapen et al., 2005, DOI: https://doi.org/10.1007/s10545-005-0015-z; Zeevaert et al., 2008, DOI: https://doi.org/10.1016/j.ymgme.2007.08.118 (wu2004mutationofthe pages 2-3, spaapen2005clinicalandbiochemical pages 3-6, zeevaert2008deficienciesinsubunits pages 3-5) |
| Molecular consequence | COG7 loss destabilizes COG complex integrity and impairs Golgi trafficking, with slowed ER-to-Golgi/Golgi transport and broad glycosylation abnormalities (wu2004mutationofthe pages 3-4, wu2004mutationofthe pages 2-3) | Wu et al., 2004, DOI: https://doi.org/10.1038/nm1041 (wu2004mutationofthe pages 3-4, wu2004mutationofthe pages 2-3) |
| Core clinical features | Severe neonatal multisystem disease: prenatal growth retardation/IUGR, microcephaly, dysmorphic facial features, loose/wrinkled skin, hypotonia, seizures/epilepsy, cholestatic liver disease/hepatopathy, recurrent infections, cardiac insufficiency, cerebellar/brain abnormalities (wu2004mutationofthe pages 1-2, zeevaert2008deficienciesinsubunits pages 2-3, zeevaert2008deficienciesinsubunits pages 3-5) | Wu et al., 2004, DOI: https://doi.org/10.1038/nm1041; Zeevaert et al., 2008, DOI: https://doi.org/10.1016/j.ymgme.2007.08.118 (wu2004mutationofthe pages 1-2, zeevaert2008deficienciesinsubunits pages 2-3, zeevaert2008deficienciesinsubunits pages 3-5) |
| Recognizable phenotype clues | Frequently highlighted pattern: microcephaly, growth impairment, adducted thumbs/hand anomalies, ventricular septal defect (VSD), and episodes of hyperthermia (zeevaert2008deficienciesinsubunits pages 3-5) | Zeevaert et al., 2008, DOI: https://doi.org/10.1016/j.ymgme.2007.08.118 (zeevaert2008deficienciesinsubunits pages 3-5) |
| Additional neurodevelopmental / structural findings | Reported features include global developmental delay, cerebral/cerebellar atrophy, hypoplasia of the corpus callosum, delayed myelination, and skeletal/hand abnormalities (unsal2026endocrineimplicationsof pages 15-16) | Ünsal & Özön, 2026, DOI: https://doi.org/10.4274/jcrpe.galenos.2025.2024-10-7 (unsal2026endocrineimplicationsof pages 15-16) |
| Transferrin IEF biomarker | Abnormal serum transferrin isoelectric focusing (IEF) showing a type II / type 2-like CDG pattern; one report described an approximately equal distribution of transferrin glycoforms with 0–4 sialic acids (wu2004mutationofthe pages 1-2, wu2004mutationofthe pages 2-3, spaapen2005clinicalandbiochemical pages 3-6, spaapen2005clinicalandbiochemical media a32196a0) | Wu et al., 2004, DOI: https://doi.org/10.1038/nm1041; Spaapen et al., 2005, DOI: https://doi.org/10.1007/s10545-005-0015-z (wu2004mutationofthe pages 1-2, wu2004mutationofthe pages 2-3, spaapen2005clinicalandbiochemical pages 3-6, spaapen2005clinicalandbiochemical media a32196a0) |
| ApoC-III IEF biomarker | Aberrant apolipoprotein C-III IEF demonstrating hyposialylation of O-linked glycans (spaapen2005clinicalandbiochemical pages 3-6, spaapen2005clinicalandbiochemical media a32196a0) | Spaapen et al., 2005, DOI: https://doi.org/10.1007/s10545-005-0015-z (spaapen2005clinicalandbiochemical pages 3-6, spaapen2005clinicalandbiochemical media a32196a0) |
| Sialic acid abnormalities | Low total plasma sialic acid reported: 321 µmol/L and 599 µmol/L in two siblings (reference 1620–2940 µmol/L); two- to fivefold reduction in total serum sialic acid also described; urinary free sialic acid increased in one patient (182 µmol/mmol creatinine) (wu2004mutationofthe pages 1-2, spaapen2005clinicalandbiochemical pages 3-6) | Wu et al., 2004, DOI: https://doi.org/10.1038/nm1041; Spaapen et al., 2005, DOI: https://doi.org/10.1007/s10545-005-0015-z (wu2004mutationofthe pages 1-2, spaapen2005clinicalandbiochemical pages 3-6) |
| Other biochemical / cellular findings | Partial N-glycan sialylation defect, decreased O-glycan sialylation, increased RCA-I lectin binding, elevated CMP-sialic acid (2–3×), reduced Golgi nucleotide-sugar transport (~30% of normal), and reduced Core1GalT (~40%) and ST3Gal-I (~62%) activities (wu2004mutationofthe pages 2-3) | Wu et al., 2004, DOI: https://doi.org/10.1038/nm1041 (wu2004mutationofthe pages 2-3) |
| Liver / muscle laboratory abnormalities | Markedly elevated transaminases in all six patients (200–890 U/L, normal <40) and elevated CK in 4/6 patients (zeevaert2008deficienciesinsubunits pages 3-5) | Zeevaert et al., 2008, DOI: https://doi.org/10.1016/j.ymgme.2007.08.118 (zeevaert2008deficienciesinsubunits pages 3-5) |
| Prognosis | Usually rapidly progressive and lethal in infancy; reported deaths occurred from 5 weeks to 9 months; initial sibling report described death at 5 and 10 weeks (wu2004mutationofthe pages 1-2, zeevaert2008deficienciesinsubunits pages 2-3, zeevaert2008deficienciesinsubunits pages 3-5) | Wu et al., 2004, DOI: https://doi.org/10.1038/nm1041; Zeevaert et al., 2008, DOI: https://doi.org/10.1016/j.ymgme.2007.08.118 (wu2004mutationofthe pages 1-2, zeevaert2008deficienciesinsubunits pages 2-3, zeevaert2008deficienciesinsubunits pages 3-5) |
| Notable populations / founder effect | Early series identified 6 patients from 4 families, all with consanguinity and originating from North Africa (2 Tunisia, 4 Morocco); shared haplotype suggested a founder effect / shared ancestral haplotype for c.169+4A>C (zeevaert2008deficienciesinsubunits pages 2-3, zeevaert2008deficienciesinsubunits pages 3-5) | Zeevaert et al., 2008, DOI: https://doi.org/10.1016/j.ymgme.2007.08.118 (zeevaert2008deficienciesinsubunits pages 2-3, zeevaert2008deficienciesinsubunits pages 3-5) |
| Frequency data available | In one screened cohort of 35 CDG-IIx cases, 5/35 (~14%) had a COG-subunit defect; COG7 was described as the most frequent COG-related defect in that series (zeevaert2008deficienciesinsubunits pages 2-3) | Zeevaert et al., 2008, DOI: https://doi.org/10.1016/j.ymgme.2007.08.118 (zeevaert2008deficienciesinsubunits pages 2-3) |
| Diagnostic practice notes | Recent CDG reviews indicate a shift from reliance on transferrin IEF alone toward WES/WGS and broader biochemical glycomics; however, transferrin IEF remains an important first-line screen for many N-glycosylation defects (francisco2023congenitaldisordersof pages 4-6, paprocka2021congenitaldisordersof pages 2-4) | Francisco et al., 2023, DOI: https://doi.org/10.1186/s13023-023-02879-z; Paprocka et al., 2021, DOI: https://doi.org/10.3390/brainsci11010088 (francisco2023congenitaldisordersof pages 4-6, paprocka2021congenitaldisordersof pages 2-4) |
| Key references | Wu et al., 2004 (Nature Medicine; discovery of lethal COG7 disorder; DOI: https://doi.org/10.1038/nm1041); Spaapen et al., 2005 (clinical/biochemical siblings report; DOI: https://doi.org/10.1007/s10545-005-0015-z); Zeevaert et al., 2008 (6-patient/founder-effect cohort; DOI: https://doi.org/10.1016/j.ymgme.2007.08.118); Francisco et al., 2023 (state-of-the-art CDG review; DOI: https://doi.org/10.1186/s13023-023-02879-z) | PMID not available in gathered evidence; URLs/DOIs supported by context (wu2004mutationofthe pages 2-3, spaapen2005clinicalandbiochemical pages 3-6, zeevaert2008deficienciesinsubunits pages 3-5, francisco2023congenitaldisordersof pages 4-6) |
Table: This table compiles the core structured facts for COG7-congenital disorder of glycosylation, including identifiers, inheritance, recurrent pathogenic variant, clinical and laboratory hallmarks, prognosis, and population observations. It is designed as a concise evidence-backed summary for knowledge-base curation.
Transferrin IEF (type II-like pattern) and apoC-III IEF (O-glycan hyposialylation) in COG7 deficiency are shown in Spaapen et al. 2005 (spaapen2005clinicalandbiochemical media a32196a0, spaapen2005clinicalandbiochemical media 9596aac9).
References
(spaapen2005clinicalandbiochemical pages 3-6): L. J. M. Spaapen, J. A. Bakker, S. B. van der Meer, H. J. Sijstermans, R. A. Steet, R. A. Wevers, and J. Jaeken. Clinical and biochemical presentation of siblings with cog-7 deficiency, a lethal multiple o- and n-glycosylation disorder. Journal of Inherited Metabolic Disease, 28:707-714, Sep 2005. URL: https://doi.org/10.1007/s10545-005-0015-z, doi:10.1007/s10545-005-0015-z. This article has 73 citations and is from a peer-reviewed journal.
(francisco2023congenitaldisordersof pages 4-6): Rita Francisco, Sandra Brasil, Joana Poejo, Jaak Jaeken, Carlota Pascoal, Paula A. Videira, and Vanessa dos Reis Ferreira. Congenital disorders of glycosylation (cdg): state of the art in 2022. Orphanet Journal of Rare Diseases, Oct 2023. URL: https://doi.org/10.1186/s13023-023-02879-z, doi:10.1186/s13023-023-02879-z. This article has 71 citations and is from a peer-reviewed journal.
(wu2004mutationofthe pages 3-4): Xiaohua Wu, Richard A Steet, Ognian Bohorov, Jaap Bakker, John Newell, Monty Krieger, Leo Spaapen, Stuart Kornfeld, and Hudson H Freeze. Mutation of the cog complex subunit gene cog7 causes a lethal congenital disorder. Nature Medicine, 10:518-523, Apr 2004. URL: https://doi.org/10.1038/nm1041, doi:10.1038/nm1041. This article has 360 citations and is from a highest quality peer-reviewed journal.
(zeevaert2008deficienciesinsubunits pages 2-3): Renate Zeevaert, François Foulquier, Jaak Jaeken, and Gert Matthijs. Deficiencies in subunits of the conserved oligomeric golgi (cog) complex define a novel group of congenital disorders of glycosylation. Molecular genetics and metabolism, 93 1:15-21, Jan 2008. URL: https://doi.org/10.1016/j.ymgme.2007.08.118, doi:10.1016/j.ymgme.2007.08.118. This article has 126 citations and is from a peer-reviewed journal.
(unsal2026endocrineimplicationsof pages 15-16): Yağmur Ünsal and Zeynep Alev Özön. Endocrine implications of congenital disorders of glycosylation. Journal of clinical research in pediatric endocrinology, Feb 2026. URL: https://doi.org/10.4274/jcrpe.galenos.2025.2024-10-7, doi:10.4274/jcrpe.galenos.2025.2024-10-7. This article has 2 citations.
(wu2004mutationofthe pages 2-3): Xiaohua Wu, Richard A Steet, Ognian Bohorov, Jaap Bakker, John Newell, Monty Krieger, Leo Spaapen, Stuart Kornfeld, and Hudson H Freeze. Mutation of the cog complex subunit gene cog7 causes a lethal congenital disorder. Nature Medicine, 10:518-523, Apr 2004. URL: https://doi.org/10.1038/nm1041, doi:10.1038/nm1041. This article has 360 citations and is from a highest quality peer-reviewed journal.
(francisco2023congenitaldisordersof pages 2-4): Rita Francisco, Sandra Brasil, Joana Poejo, Jaak Jaeken, Carlota Pascoal, Paula A. Videira, and Vanessa dos Reis Ferreira. Congenital disorders of glycosylation (cdg): state of the art in 2022. Orphanet Journal of Rare Diseases, Oct 2023. URL: https://doi.org/10.1186/s13023-023-02879-z, doi:10.1186/s13023-023-02879-z. This article has 71 citations and is from a peer-reviewed journal.
(wu2004mutationofthe pages 1-2): Xiaohua Wu, Richard A Steet, Ognian Bohorov, Jaap Bakker, John Newell, Monty Krieger, Leo Spaapen, Stuart Kornfeld, and Hudson H Freeze. Mutation of the cog complex subunit gene cog7 causes a lethal congenital disorder. Nature Medicine, 10:518-523, Apr 2004. URL: https://doi.org/10.1038/nm1041, doi:10.1038/nm1041. This article has 360 citations and is from a highest quality peer-reviewed journal.
(zeevaert2008deficienciesinsubunits pages 3-5): Renate Zeevaert, François Foulquier, Jaak Jaeken, and Gert Matthijs. Deficiencies in subunits of the conserved oligomeric golgi (cog) complex define a novel group of congenital disorders of glycosylation. Molecular genetics and metabolism, 93 1:15-21, Jan 2008. URL: https://doi.org/10.1016/j.ymgme.2007.08.118, doi:10.1016/j.ymgme.2007.08.118. This article has 126 citations and is from a peer-reviewed journal.
(wu2004mutationofthe pages 4-6): Xiaohua Wu, Richard A Steet, Ognian Bohorov, Jaap Bakker, John Newell, Monty Krieger, Leo Spaapen, Stuart Kornfeld, and Hudson H Freeze. Mutation of the cog complex subunit gene cog7 causes a lethal congenital disorder. Nature Medicine, 10:518-523, Apr 2004. URL: https://doi.org/10.1038/nm1041, doi:10.1038/nm1041. This article has 360 citations and is from a highest quality peer-reviewed journal.
(spaapen2005clinicalandbiochemical pages 1-3): L. J. M. Spaapen, J. A. Bakker, S. B. van der Meer, H. J. Sijstermans, R. A. Steet, R. A. Wevers, and J. Jaeken. Clinical and biochemical presentation of siblings with cog-7 deficiency, a lethal multiple o- and n-glycosylation disorder. Journal of Inherited Metabolic Disease, 28:707-714, Sep 2005. URL: https://doi.org/10.1007/s10545-005-0015-z, doi:10.1007/s10545-005-0015-z. This article has 73 citations and is from a peer-reviewed journal.
(francisco2023congenitaldisordersof pages 1-2): Rita Francisco, Sandra Brasil, Joana Poejo, Jaak Jaeken, Carlota Pascoal, Paula A. Videira, and Vanessa dos Reis Ferreira. Congenital disorders of glycosylation (cdg): state of the art in 2022. Orphanet Journal of Rare Diseases, Oct 2023. URL: https://doi.org/10.1186/s13023-023-02879-z, doi:10.1186/s13023-023-02879-z. This article has 71 citations and is from a peer-reviewed journal.
(spaapen2005clinicalandbiochemical media a32196a0): L. J. M. Spaapen, J. A. Bakker, S. B. van der Meer, H. J. Sijstermans, R. A. Steet, R. A. Wevers, and J. Jaeken. Clinical and biochemical presentation of siblings with cog-7 deficiency, a lethal multiple o- and n-glycosylation disorder. Journal of Inherited Metabolic Disease, 28:707-714, Sep 2005. URL: https://doi.org/10.1007/s10545-005-0015-z, doi:10.1007/s10545-005-0015-z. This article has 73 citations and is from a peer-reviewed journal.
(spaapen2005clinicalandbiochemical media 9596aac9): L. J. M. Spaapen, J. A. Bakker, S. B. van der Meer, H. J. Sijstermans, R. A. Steet, R. A. Wevers, and J. Jaeken. Clinical and biochemical presentation of siblings with cog-7 deficiency, a lethal multiple o- and n-glycosylation disorder. Journal of Inherited Metabolic Disease, 28:707-714, Sep 2005. URL: https://doi.org/10.1007/s10545-005-0015-z, doi:10.1007/s10545-005-0015-z. This article has 73 citations and is from a peer-reviewed journal.
(paprocka2021congenitaldisordersof pages 2-4): Justyna Paprocka, Aleksandra Jezela-Stanek, Anna Tylki-Szymańska, and Stephanie Grunewald. Congenital disorders of glycosylation from a neurological perspective. Brain Sciences, 11:88, Jan 2021. URL: https://doi.org/10.3390/brainsci11010088, doi:10.3390/brainsci11010088. This article has 131 citations.
(NCT04199000 chunk 1): Eva Morava-Kozicz. Clinical and Basic Investigations Into Congenital Disorders of Glycosylation. Icahn School of Medicine at Mount Sinai. 2019. ClinicalTrials.gov Identifier: NCT04199000