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COG7-congenital disorder of glycosylation

COG7–Congenital Disorder of Glycosylation (COG7-CDG) — Comprehensive Research Report

2026-05-09
Falcon MONDO:0012118 Model: Edison Scientific Literature 29 citations

COG7–Congenital Disorder of Glycosylation (COG7-CDG) — Comprehensive Research Report

Target disease

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).

1. Disease information

Overview (current understanding)

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).

Synonyms / alternative names

Key identifiers (from available evidence)

Not found in retrieved texts for this run: Orphanet number, ICD-10/ICD-11 code, MeSH disease heading, MONDO ID.

Evidence provenance

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).

2. Etiology

Disease causal factors

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).

Risk factors

  • Genetic: COG7 loss-of-function variants; a recurrent splice variant is associated with multiple families (zeevaert2008deficienciesinsubunits pages 3-5).
  • Environmental: Not established/expected as a primary driver in this Mendelian disorder; no gene–environment interaction evidence was identified in retrieved sources.

Protective factors

No genetic or environmental protective factors were identified in retrieved sources.

3. Phenotypes (clinical spectrum)

Typical onset, course, and severity

COG7-CDG is classically a rapidly progressive neonatal multisystem disorder with early lethality (weeks to months) (wu2004mutationofthe pages 1-2, zeevaert2008deficienciesinsubunits pages 3-5).

Key clinical manifestations (human)

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)

Frequency information (available)

Quality of life impact

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).

4. Genetic / molecular information

Causal gene

Pathogenic variants (human)

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).

Modifier genes / epigenetics / chromosomal abnormalities

No modifier genes, epigenetic mechanisms, or chromosomal abnormalities specific to COG7-CDG were identified in retrieved sources.

5. Environmental information

COG7-CDG is a monogenic disorder; non-genetic environmental contributors or infectious triggers were not reported in the retrieved evidence.

6. Mechanism / pathophysiology

Mechanistic causal chain (gene → cell biology → biochemical signature → clinical phenotype)

  1. COG7 deficiency reduces/abolishes COG7 protein and destabilizes the COG complex (wu2004mutationofthe pages 2-3).
  2. This impairs ER–Golgi and intra-Golgi trafficking (e.g., slowed trafficking of a Golgi sialyltransferase reporter ST-GFP) (wu2004mutationofthe pages 2-3, wu2004mutationofthe pages 3-4).
  3. Disrupted Golgi homeostasis leads to defective glycosylation enzyme function/localization, including reduced activities of O-glycan Core1GalT and ST3Gal-I and impaired nucleotide-sugar transport into the Golgi (~30% of normal in patient fibroblasts) (wu2004mutationofthe pages 2-3).
  4. The net result is combined N- and O-hypoglycosylation, especially hyposialylation/galactosylation defects, measurable in plasma glycoproteins (transferrin, apoC-III) and reflected in systemic multi-organ disease (wu2004mutationofthe pages 2-3, spaapen2005clinicalandbiochemical pages 3-6).

Key cellular/biochemical findings (selected quantitative data)

Ontology suggestions

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).

7. Anatomical structures affected

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).

8. Temporal development

9. Inheritance and population

Inheritance

Autosomal recessive, frequently in consanguineous families (zeevaert2008deficienciesinsubunits pages 2-3, zeevaert2008deficienciesinsubunits pages 3-5).

Epidemiology (available data)

Population prevalence/incidence estimates were not identified in retrieved evidence.

Variant distribution / founder effect

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).

Case fatality / prognosis statistics

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).

10. Diagnostics

Core clinical laboratory tests / biomarkers

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).

Genetic testing

Disease confirmation is via molecular detection of biallelic COG7 pathogenic variants (e.g., IVS1+4A>C) (wu2004mutationofthe pages 2-3, spaapen2005clinicalandbiochemical pages 3-6).

Current diagnostic practice trends (2023–2024 emphasis)

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).

Differential diagnosis

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).

11. Outcome / prognosis

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).

12. Treatment

Disease-specific therapy

No COG7-CDG-specific disease-modifying therapy was identified in the retrieved evidence.

General CDG treatment landscape (expert consensus from authoritative reviews)

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).

Supportive care (real-world implementations; inferred from phenotype)

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).

Clinical trials / registries relevant to CDG (and applicability to COG7-CDG)

  • NCT04199000 (“Clinical and Basic Investigations Into Congenital Disorders of Glycosylation”), observational natural history study; start date 2019-10-08; recruiting; estimated enrollment 500. Key aims include measuring progression/severity using the Nijmegen CDG rating scale and collecting patient-reported outcomes (PROMIS) and biospecimens for biomarkers (NCT04199000 chunk 1). The record requires a genetically/enzymatically/molecularly confirmed CDG diagnosis, making it plausibly inclusive of rare CDG subtypes even if COG7 is not explicitly listed among keywords in the excerpt (NCT04199000 chunk 1).

MAXO suggestions (supportive)

13. Prevention

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).

14. Other species / natural disease

No naturally occurring veterinary disease analogs specifically tied to COG7 were identified in retrieved sources.

15. Model organisms and experimental systems

Cellular models (human)

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).

Comparative models

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).

Recent developments and latest research emphasis (2023–2024)

Field-level advances relevant to COG7-CDG

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).

Key structured summary table

Table (click to expand)
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.

Key diagnostic figure evidence (visual)

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).

Evidence gaps / not available in retrieved sources

  • MONDO, Orphanet, ICD-10/ICD-11, and MeSH identifiers for COG7-CDG were not found in retrieved texts during this run.
  • Population prevalence/incidence and long-term survivorship data beyond infancy were not identified.
  • No COG7-specific interventional trials were identified; available trial evidence is CDG-wide natural history/registry infrastructure.

References

  1. (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.

  2. (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.

  3. (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.

  4. (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.

  5. (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.

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  7. (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.

  8. (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.

  9. (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.

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  11. (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.

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  15. (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.

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