TUBGCP6-related Microcephaly and Chorioretinopathy

👪

Inheritance

1

Autosomal recessive inheritance HP:0000007

Affected individuals have biallelic TUBGCP6 variants. Reported families include homozygous and compound-heterozygous states; compound heterozygosity is therefore one observed configuration, not a disease-wide requirement.

Autosomal recessive inheritance

Show evidence (1 reference)

PMID:37031378 SUPPORT Human Clinical

"Autosomal recessive microcephaly and chorioretinopathy-1 (MCCRP1) is a rare Mendelian disorder resulting from biallelic loss of function variants in Tubulin-Gamma Complex Associated Protein 6 (TUBGCP6, MIM#610053)."

Directly states the recessive, biallelic disease association.

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Discussions and Knowledge Gaps

1

Do biallelic patient alleles reproduce the acute TUBGCP6-depletion phenotype in neural and retinal developmental systems, and which cellular defect drives each organ phenotype?

KNOWLEDGE GAP OPEN gap_tubgcp6_patient_allele_and_developmental_models

Attached to

pathophysiology#Reduced TUBGCP6 Function pathophysiology#Reduced Cell Proliferation pathophysiology#Abnormal Cerebral Development pathophysiology#Abnormal Chorioretinal Development

Acute loss of endogenously tagged TUBGCP6 in DLD-1 cells has a specific, rescuable effect on centriole duplication and also reduces nucleation and proliferation. The model does not contain a disease allele and is neither neural nor retinal. Human reports establish the brain and eye endpoints but do not measure the intervening mechanism. Patient-derived cells, cerebral or retinal organoids, and allele-specific rescue experiments are needed to test the bridge and to distinguish effects of nucleation, centriole duplication, mitotic arrest, and other unknown intermediates.

Show evidence (2 references)

PMID:31874114 SUPPORT In Vitro

"Expression of a TUBGCP6 transgene fully rescued centriole duplication in auxin-treated TUBGCP6AID cells, demonstrating that this transgene was able to functionally compensate for the loss of the endogenous protein (Fig. S5, F and G)."

Establishes a specific rescuable cellular phenotype in the acute DLD-1 model.

PMID:37031378 SUPPORT Human Clinical

"Clinical features of this disorder include microcephaly, cognitive impairment, dysmorphic features, and variable ophthalmological anomalies including chorioretinopathy."

Establishes the human endpoints without testing the cellular bridge.

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Pathophysiology

8

Reduced TUBGCP6 Function

The 2023 disease review describes biallelic TUBGCP6 variants as loss-of-function, and reported alleles include sequence changes and deletions. That disease-level assignment still requires allele-level calibration: the founding p.Ter1820Gly read-through allele was predicted to extend the protein or promote non-stop-mediated decay but was not functionally tested in the founding report. Acute depletion of TUBGCP6 in DLD-1 cells models reduced protein availability, not any specific patient genotype.

TUBGCP6 hgnc:18127

Genetic context allele_type: reported sequence and deletion alleles with predicted or asserted loss of function variant_origin: GERMLINE functional_impact_category: LOSS_OF_FUNCTION

Biallelic variants are required, but the allelic configuration varies among families. The disease literature assigns loss of function broadly, but p.Ter1820Gly remains a predicted rather than experimentally demonstrated loss-of-function allele.

gamma-tubulin ring complex GO:0000931

Downstream

Reduced Centrosome-Driven Microtubule Nucleation Acute loss of TUBGCP6 reduced centrosome-driven microtubule nucleation in DLD-1 cells. Application to germline patient alleles is model extrapolation.

Centriole Duplication Failure Acute endogenous TUBGCP6 degradation caused centriole-duplication failure in DLD-1 cells, and a TUBGCP6 transgene rescued that experimental defect.

Show evidence (4 references)

PMID:37031378 SUPPORT Human Clinical

"Autosomal recessive microcephaly and chorioretinopathy-1 (MCCRP1) is a rare Mendelian disorder resulting from biallelic loss of function variants in Tubulin-Gamma Complex Associated Protein 6 (TUBGCP6, MIM#610053)."

Supports the disease-level biallelic loss-of-function assignment.

PMID:39634241 SUPPORT Human Clinical

"Compound heterozygous variants were identified in TUBGCP6 including an eleven base pair deletion (inherited from father) and 405 base pair large deletion (inherited from mother)."

Documents two deletion alleles in trans in an affected family.

PMID:22279524 SUPPORT Human Clinical

"This read-through variant is predicted to incorporate 16 extra amino acids at the C-terminus of TUBGCP6 and/or may accelerate mRNA degradation via non-stop mediated decay."

Supports a predicted function-reducing mechanism for the founding allele while making clear that the mechanism was predictive, not experimentally demonstrated.

+ 1 more reference

Reduced Centrosome-Driven Microtubule Nucleation

Acute degradation of endogenously tagged TUBGCP6 in DLD-1 cells reduced centrosome-driven microtubule nucleation. This is a direct cellular assay in a colon-cancer cell line; neither neural nor retinal progenitors were tested.

microtubule nucleation GO:0007020 ↓ DECREASED

Downstream

Monopolar-Spindle Mitotic Arrest Reduced nucleation and monopolar-spindle arrest co-occurred after the same depletion; the experiment did not isolate nucleation as the sole mediator.

Show evidence (1 reference)

PMID:31874114 SUPPORT In Vitro

"Cells depleted of TUBGCP6 also exhibited mitotic defects similar to those observed following loss of WBP11, including reduced centrosome-driven microtubule nucleation and mitotic arrest with a monopolar spindle (Fig. 2, G and H; Fig. 7, E–G; and Videos 5 and 6)."

Directly reports reduced centrosome-driven microtubule nucleation.

Centriole Duplication Failure

Acute degradation of both endogenously tagged TUBGCP6 alleles in DLD-1 cells produced a pronounced failure of centriole duplication. Rescue by a TUBGCP6 transgene supports perturbation specificity, but this remains an acute cell-line model rather than a germline patient-allele assay.

centriole replication GO:0007099 ↓ DECREASED

Downstream

Monopolar-Spindle Mitotic Arrest Centriole-duplication failure and monopolar-spindle arrest co-occurred after TUBGCP6 depletion, but the paper did not isolate their causal ordering.

Show evidence (2 references)

PMID:31874114 SUPPORT In Vitro

"Degradation of TUBGCP6 led to a pronounced failure of centriole duplication that was similar to that observed in WBP11AID cells (Fig. 7, A–C)."

Directly reports centriole-duplication failure after TUBGCP6 loss.

PMID:31874114 SUPPORT In Vitro

"Expression of a TUBGCP6 transgene fully rescued centriole duplication in auxin-treated TUBGCP6AID cells, demonstrating that this transgene was able to functionally compensate for the loss of the endogenous protein (Fig. S5, F and G)."

Rescue supports specificity of the acute TUBGCP6-depletion phenotype.

Monopolar-Spindle Mitotic Arrest

TUBGCP6-depleted DLD-1 cells developed mitotic arrest with a monopolar spindle and predominantly underwent mitotic slippage at later observation times. These are in-vitro cell-division phenotypes.

mitotic spindle organization GO:0007052 ↕ DYSREGULATED

Downstream

Reduced Cell Proliferation The mitotic deficits reduced proliferation in the same cell model.

Show evidence (1 reference)

PMID:31874114 SUPPORT In Vitro

"Cells depleted of TUBGCP6 also exhibited mitotic defects similar to those observed following loss of WBP11, including reduced centrosome-driven microtubule nucleation and mitotic arrest with a monopolar spindle (Fig. 2, G and H; Fig. 7, E–G; and Videos 5 and 6)."

Directly reports the monopolar-spindle mitotic arrest phenotype.

Reduced Cell Proliferation

Acute TUBGCP6 depletion dramatically reduced proliferation of DLD-1 cells. Reduced developmental progenitor output is a plausible bridge to the brain, chorioretinal, and somatic-growth endpoints, but that bridge has not been tested in patient-derived, neural, or retinal models.

cell population proliferation GO:0008283 ↓ DECREASED

Downstream

Abnormal Cerebral Development The cellular model and human cerebral phenotype are consistent with this bridge, but no TUBGCP6 neural-development experiment establishes it.

Abnormal Chorioretinal Development The cellular model and human chorioretinal phenotype are consistent with this bridge, but no TUBGCP6 retinal-development experiment establishes it.

Reduced Somatic Growth Short stature is reported clinically, but the cellular-to-organism growth bridge has not been tested for TUBGCP6 patient variants.

Show evidence (1 reference)

PMID:31874114 SUPPORT In Vitro

"Similar to WBP11AID cells, the mitotic deficits dramatically reduced the proliferation of cells depleted of TUBGCP6 (Fig. 7 H)."

Directly reports reduced proliferation in TUBGCP6-depleted cells.

Abnormal Cerebral Development

Human findings include congenital severe microcephaly, diffuse pachygyria, small cerebral hemispheres, cerebellar vermis hypoplasia, developmental and intellectual impairment, and occasional seizures. Later reports extend the imaging spectrum to agyria/pachygyria, ventriculomegaly, and abnormal sulcation. These observations define the tissue endpoint rather than proving the upstream cellular bridge.

Downstream

Microcephaly Reduced cerebral growth presents as congenital microcephaly.

Global Developmental Delay Developmental delay is part of the reported cerebral phenotype.

Intellectual Disability Intellectual impairment accompanies the congenital brain phenotype.

Pachygyria Pachygyria is a directly imaged cortical malformation.

Hypoplasia of the Corpus Callosum At this tissue-to-phenotype graph scale, reduced callosal area is an observed structural manifestation of abnormal cerebral development. This does not establish the upstream cellular mechanism or a disease-wide frequency.

Cerebellar Vermis Hypoplasia A hypoplastic vermis is a directly imaged structural manifestation at the cerebral-development tissue endpoint.

Seizure Seizures occurred in a minority of the original cohort.

Show evidence (2 references)

PMID:22279524 SUPPORT Human Clinical

"Magnetic resonance imaging shows diffuse pachygyria (Figure 2, C). The cerebral hemispheres are small relative to the cerebellum, which has a hypoplastic vermis (Figure 2, D)."

Directly documents the cerebral malformation pattern in the original cohort.

PMID:39634241 SUPPORT Human Clinical

"We report third trimester microcephaly with ventriculomegaly and abnormal sulcation as part of the antenatal presentation for this condition."

Extends the prenatal cerebral-imaging spectrum in one family.

Abnormal Chorioretinal Development

The original cohort had underdeveloped retina and choroid with focal areas of bare sclera, scalloped retina, abnormal peripheral tissue, vitreoretinal traction, and risk of retinal detachment. This anatomy is better represented by broad abnormal chorioretinal morphology than by assuming a uniform progressive dystrophy.

Downstream

Chorioretinopathy Underdeveloped retina and choroid produce the defining ocular morphology.

Visual Impairment The ocular abnormality is accompanied by early visual impairment.

Retinal Detachment Vitreoretinal traction creates points at risk for retinal detachment.

Show evidence (1 reference)

PMID:22279524 SUPPORT Human Clinical

"The retina and choroid are underdeveloped and have focal defects that reveal bare sclera."

Directly describes abnormal chorioretinal development.

Reduced Somatic Growth

Short stature is reported in TUBGCP6-affected individuals, including the proband with compound-heterozygous deletion alleles. The relationship to the DLD-1 proliferation phenotype is plausible but untested.

Downstream

Short Stature Reduced somatic growth is clinically expressed as short stature.

Show evidence (2 references)

PMID:39634241 SUPPORT Human Clinical

"We present the first Indian family with an affected child and sibling fetus with microcephaly, dysmorphism, and agyria/pachygyria complex on brain imaging in both and short stature, intellectual disability, and visual impairment in proband."

Directly reports short stature in the affected proband.

PMID:25344692 SUPPORT Human Clinical

"Here we identify mutations in the genes encoding PLK4 kinase, a master regulator of centriole duplication, and its substrate TUBGCP6 in individuals with microcephalic primordial dwarfism and additional congenital anomalies, including retinopathy, thereby extending the human phenotypic spectrum..."

Supports growth restriction in the combined PLK4/TUBGCP6 ascertainment; the source abstract does not separate gene-specific counts.

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Pathograph

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Phenotypes

12

Eye 3

Chorioretinopathy Abnormal chorioretinal morphology HP:0000532

Show evidence (1 reference)

PMID:22279524 SUPPORT Human Clinical

"The retina and choroid are underdeveloped and have focal defects that reveal bare sclera."

Directly describes the chorioretinal morphology.

Visual Impairment HP:0000505

Show evidence (1 reference)

PMID:37031378 SUPPORT Human Clinical

"visual impairment becomes evident during the first year of life"

Directly reports early visual impairment.

Retinal Detachment HP:0000541

Show evidence (1 reference)

PMID:22279524 SUPPORT Human Clinical

"Condensations of vitreous may attach to the retina in transition regions between scalloped and gray tissue, marking points of traction for retinal detachment."

Directly describes traction associated with retinal detachment.

Head and Neck 2

Microcephaly HP:0000252

Show evidence (1 reference)

PMID:22279524 SUPPORT Human Clinical

"All patients are born with microcephaly, a sloping forehead, diminutive anterior fontanelle, and sutural ridging (Figure 2, A)."

Directly documents congenital microcephaly in the original cohort.

Sloping Forehead HP:0000340

Show evidence (1 reference)

PMID:22279524 SUPPORT Human Clinical

"All patients are born with microcephaly, a sloping forehead, diminutive anterior fontanelle, and sutural ridging (Figure 2, A)."

Directly reports sloping forehead in the founding cohort.

Nervous System 6

Intellectual Disability HP:0001249

Show evidence (1 reference)

PMID:39634241 SUPPORT Human Clinical

"We present the first Indian family with an affected child and sibling fetus with microcephaly, dysmorphism, and agyria/pachygyria complex on brain imaging in both and short stature, intellectual disability, and visual impairment in proband."

Directly reports intellectual disability in the affected proband.

Global Developmental Delay HP:0001263

Show evidence (1 reference)

PMID:22279524 SUPPORT Human Clinical

"Children walk independently between 14 and 36 months of age and language emerges at an appropriate age but remains rudimentary."

Documents delayed walking and limited language development.

Pachygyria HP:0001302

Show evidence (1 reference)

PMID:22279524 SUPPORT Human Clinical

"Magnetic resonance imaging shows diffuse pachygyria (Figure 2, C)."

Directly reports diffuse pachygyria on MRI.

Hypoplasia of the Corpus Callosum HP:0002079

Show evidence (1 reference)

PMID:22279524 SUPPORT Human Clinical

"area of the corpus callosum is approximately half that of an age- matched control child (2.75 cm 2 versus 5.61 cm 2)."

Supports reduced callosal size in one child; the hypoplasia term is an anatomical interpretation rather than source wording.

Cerebellar Vermis Hypoplasia HP:0001320

Show evidence (1 reference)

PMID:22279524 SUPPORT Human Clinical

"The cerebral hemispheres are small relative to the cerebellum, which has a hypoplastic vermis (Figure 2, D)."

Directly reports cerebellar vermis hypoplasia on MRI.

Seizure 2/9 (22%) in the original Mennonite cohort HP:0001250

Show evidence (1 reference)

PMID:22279524 SUPPORT Human Clinical

"Two of nine patients (22%) have epilepsy: one started having drop attacks in late childhood and another developed nocturnal epilepsy as an adult."

Gives the exact cohort-specific count and seizure presentations.

Growth 1

Short Stature HP:0004322

Show evidence (1 reference)

PMID:39634241 SUPPORT Human Clinical

"We present the first Indian family with an affected child and sibling fetus with microcephaly, dysmorphism, and agyria/pachygyria complex on brain imaging in both and short stature, intellectual disability, and visual impairment in proband."

Directly reports short stature in the affected proband.

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Genetic Associations

1

TUBGCP6 (Causative)

Gene: TUBGCP6 (tubulin gamma complex associated protein 6) hgnc:18127

Show evidence (1 reference)

PMID:37031378 SUPPORT Human Clinical

"biallelic loss of function variants in Tubulin-Gamma Complex Associated Protein 6 (TUBGCP6, MIM#610053)"

Names TUBGCP6 as the biallelic causative gene.

💊

Medical Actions

1

Genetic Counseling

Action: Genetic Counseling NCIT:C15240

Establishing the biallelic TUBGCP6 diagnosis can inform family reproductive planning. The cited source supports that management consequence but does not state a numeric recurrence risk, surveillance schedule, or treatment outcome, so none is asserted here.

Show evidence (1 reference)

PMID:37031378 SUPPORT Human Clinical

"it is important to recognize and diagnose this syndrome in view of its impact on patient health management and familial reproductive plans"

Supports reproductive-planning implications of molecular recognition; it does not provide a counseling protocol or a numeric recurrence figure.

🔬

Diagnosis

2

Ophthalmological examination

Ophthalmological assessment can characterize the retina, choroid, and vitreoretinal interface. The original description documents underdevelopment, focal defects, and traction associated with detachment rather than one uniform dystrophic pattern.

eye examination NCIT:C38060

Show evidence (1 reference)

PMID:22279524 SUPPORT Human Clinical

"The retina and choroid are underdeveloped and have focal defects that reveal bare sclera."

Documents the ocular anatomy that ophthalmological evaluation must characterize.

Sequence and structural-variant-sensitive genetic testing

Confirmation requires two pathogenic TUBGCP6 alleles. Testing should be able to detect small sequence variants and deletions or other structural variants; genome sequencing identified an 11-base-pair deletion in trans with a 405-base-pair deletion in one family.

genetic testing NCIT:C15709

Show evidence (1 reference)

PMID:39634241 SUPPORT Human Clinical

"Genome sequencing through the Indian Undiagnosed Disease Program (I-UDP) confirmed the diagnosis in both proband and sibling fetus. Compound heterozygous variants were identified in TUBGCP6 including an eleven base pair deletion (inherited from father) and 405 base pair large deletion (inherited..."

Directly supports genome sequencing and deletion-sensitive analysis for molecular confirmation.

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Imaging Findings

3

Diffuse pachygyria on brain MRI

Diffuse pachygyria was documented by MRI in the original cohort.

Mri Diffuse

Pachygyria HP:0001302 brain UBERON:0000955

Show evidence (1 reference)

PMID:22279524 SUPPORT Human Clinical

"Microcephaly with chorioretinopathy. The phenotype was originally described by Victor McKusick ... Magnetic resonance imaging shows diffuse pachygyria (Figure 2, C). ... Microcephaly and chorioretinopathy due to a homozygous TUBGCP6 mutation."

Retains the diffuse-pachygyria observation and restores the microcephaly/chorioretinopathy context and the figure's explicit TUBGCP6 attribution. Ellipses mark omitted source text in order.

Cerebellar vermis hypoplasia on brain MRI

A hypoplastic cerebellar vermis accompanied small cerebral hemispheres on MRI.

Mri

Cerebellar vermis hypoplasia HP:0001320 cerebellar vermis UBERON:0004720

Show evidence (1 reference)

PMID:22279524 SUPPORT Human Clinical

"The cerebral hemispheres are small relative to the cerebellum, which has a hypoplastic vermis (Figure 2, D)."

Directly reports cerebellar vermis hypoplasia on MRI.

Prenatal ventriculomegaly and abnormal sulcation on fetal imaging

Ventriculomegaly and abnormal sulcation were reported in the third trimester. The cached abstract does not identify the imaging modality, so OTHER is used rather than inferring ultrasound or MRI.

Other

Ventriculomegaly HP:0002119 brain UBERON:0000955

Show evidence (1 reference)

PMID:39634241 SUPPORT Human Clinical

"We report third trimester microcephaly with ventriculomegaly and abnormal sulcation as part of the antenatal presentation for this condition."

Directly reports the prenatal findings without specifying modality.

🌍

Epidemiology

2

Molecularly confirmed cases reported before the 2023 series

The 2023 review stated that seven molecularly confirmed patients from five unrelated families had previously been reported. This is a literature case count, not a population prevalence estimate.

Show evidence (1 reference)

PMID:37031378 SUPPORT Human Clinical

"To date, only seven molecularly confirmed patients from five unrelated families have been reported."

Gives the source-specific pre-existing case and family count.

Cases added by the 2023 series

The 2023 report added four unrelated patients, including one prenatal diagnosis. This report-specific increment is kept separate from the prior case count to avoid an inferred pooled denominator.

Show evidence (1 reference)

PMID:37031378 SUPPORT Human Clinical

"We report an additional four unrelated patients with TUBGCP6 variants including one prenatal diagnosis and review the clinical phenotypes and genotypes of all the known cases."

Gives the report-specific increment and prenatal case.

🔀

Differential Diagnoses

4

Conditions with similar clinical presentations that must be differentiated from TUBGCP6-related Microcephaly and Chorioretinopathy:

Congenital toxoplasmosis or cytomegalovirus infection

Overlapping Features Acquired congenital infection can combine microcephaly with chorioretinal abnormalities. Infection testing and demonstration of biallelic TUBGCP6 variants distinguish these acquired conditions from MCCRP1.

Distinguishing Features

MCCRP1 is confirmed by biallelic TUBGCP6 variants.

Show evidence (1 reference)

PMID:37031378 SUPPORT Human Clinical

"The clinical presentation resembles the findings in some acquired conditions such as congenital toxoplasmosis and cytomegalovirus infections; thus, it is important to recognize and diagnose this syndrome in view of its impact on patient health management and familial reproductive plans."

Directly identifies the acquired-infection differential.

{ }

Source YAML

click to show

name: TUBGCP6-related Microcephaly and Chorioretinopathy
creation_date: "2026-08-20T17:45:00Z"
category: Mendelian
disease_term:
preferred_term: microcephaly and chorioretinopathy 1
term:
id: MONDO:0009624
label: microcephaly and chorioretinopathy 1
description: >-
TUBGCP6-related microcephaly and chorioretinopathy (MCCRP1) is a rare
autosomal-recessive neuro-ophthalmic disorder caused by biallelic TUBGCP6
variants. The reported phenotype combines congenital microcephaly and
neurodevelopmental impairment with variable chorioretinal abnormalities and
visual impairment. Short stature, pachygyria or abnormal sulcation,
ventriculomegaly, cerebellar vermis hypoplasia, seizures, and retinal
detachment have each been reported in source-specific cohorts or families.

TUBGCP6 encodes a component of the gamma-tubulin ring complex. In DLD-1 cells,
acute experimental degradation of endogenous TUBGCP6 causes parallel defects
in centriole duplication and centrosome-driven microtubule nucleation, with
monopolar-spindle mitotic arrest and reduced proliferation. These experiments
establish cellular functions of TUBGCP6 but do not test patient alleles or
neural or retinal developmental models, so the bridge from the cellular
phenotype to the human brain and eye manifestations remains indirect.

The combination of microcephaly and chorioretinopathy can resemble congenital
toxoplasmosis or cytomegalovirus infection. Molecular confirmation is
important because reported alleles include small sequence changes and a
structural deletion detected by genome sequencing.
parents:
- hereditary disease
- congenital nervous system disorder
- eye disease
references:
- reference: PMID:37031378
title: "Biallelic variants in TUBGCP6 result in microcephaly and chorioretinopathy 1: Report of four cases and a literature review."
- reference: PMID:39634241
title: Two-Compound Heterozygous Deletions Affecting TUBGCP6 in a Patient with Microcephaly and Ocular Abnormalities and in an Unborn Sibling with Abnormal Sulcation.
- reference: PMID:22279524
title: Genetic mapping and exome sequencing identify variants associated with five novel diseases.
- reference: PMID:25344692
title: Mutations in PLK4, encoding a master regulator of centriole biogenesis, cause microcephaly, growth failure and retinopathy.
- reference: PMID:31874114
title: WBP11 is required for splicing the TUBGCP6 pre-mRNA to promote centriole duplication.
- reference: PMID:25124931
title: Phenotypic overlap between familial exudative vitreoretinopathy and microcephaly, lymphedema, and chorioretinal dysplasia caused by KIF11 mutations.
- reference: PMID:25817018
title: Mutations in TUBGCP4 alter microtubule organization via the γ-tubulin ring complex in autosomal-recessive microcephaly with chorioretinopathy.
inheritance:
- name: Autosomal recessive inheritance
inheritance_term:
preferred_term: Autosomal recessive inheritance
term:
id: HP:0000007
label: Autosomal recessive inheritance
description: >-
Affected individuals have biallelic TUBGCP6 variants. Reported families
include homozygous and compound-heterozygous states; compound heterozygosity
is therefore one observed configuration, not a disease-wide requirement.
evidence:
- reference: PMID:37031378
reference_title: "Biallelic variants in TUBGCP6 result in microcephaly and chorioretinopathy 1: Report of four cases and a literature review."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Autosomal recessive microcephaly and chorioretinopathy-1 (MCCRP1) is a rare
Mendelian disorder resulting from biallelic loss of function variants in
Tubulin-Gamma Complex Associated Protein 6 (TUBGCP6, MIM#610053).
explanation: Directly states the recessive, biallelic disease association.
pathophysiology:
- name: Reduced TUBGCP6 Function
role: TRIGGER
biological_scale: MOLECULAR
description: >-
The 2023 disease review describes biallelic TUBGCP6 variants as
loss-of-function, and reported alleles include sequence changes and
deletions. That disease-level assignment still requires allele-level
calibration: the founding p.Ter1820Gly read-through allele was predicted to
extend the protein or promote non-stop-mediated decay but was not
functionally tested in the founding report. Acute depletion of TUBGCP6 in
DLD-1 cells models reduced protein availability, not any specific patient
genotype.
genetic_context:
functional_impact_category: LOSS_OF_FUNCTION
variant_origin: GERMLINE
allele_type: reported sequence and deletion alleles with predicted or asserted loss of function
description: >-
Biallelic variants are required, but the allelic configuration varies
among families. The disease literature assigns loss of function broadly,
but p.Ter1820Gly remains a predicted rather than experimentally
demonstrated loss-of-function allele.
genes:
- preferred_term: TUBGCP6
term:
id: hgnc:18127
label: TUBGCP6
cellular_components:
- preferred_term: gamma-tubulin ring complex
term:
id: GO:0000931
label: gamma-tubulin ring complex
evidence:
- reference: PMID:37031378
reference_title: "Biallelic variants in TUBGCP6 result in microcephaly and chorioretinopathy 1: Report of four cases and a literature review."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Autosomal recessive microcephaly and chorioretinopathy-1 (MCCRP1) is a rare
Mendelian disorder resulting from biallelic loss of function variants in
Tubulin-Gamma Complex Associated Protein 6 (TUBGCP6, MIM#610053).
explanation: Supports the disease-level biallelic loss-of-function assignment.
- reference: PMID:39634241
reference_title: Two-Compound Heterozygous Deletions Affecting TUBGCP6 in a Patient with Microcephaly and Ocular Abnormalities and in an Unborn Sibling with Abnormal Sulcation.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Compound heterozygous variants were identified in TUBGCP6 including an
eleven base pair deletion (inherited from father) and 405 base pair large
deletion (inherited from mother).
explanation: Documents two deletion alleles in trans in an affected family.
- reference: PMID:22279524
reference_title: Genetic mapping and exome sequencing identify variants associated with five novel diseases.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
This read-through variant is predicted to incorporate 16 extra amino acids
at the C-terminus of TUBGCP6 and/or may accelerate mRNA degradation via
non-stop mediated decay.
explanation: >-
Supports a predicted function-reducing mechanism for the founding allele
while making clear that the mechanism was predictive, not experimentally
demonstrated.
- reference: PMID:31874114
reference_title: WBP11 is required for splicing the TUBGCP6 pre-mRNA to promote centriole duplication.
supports: SUPPORT
evidence_source: IN_VITRO
snippet: >-
TUBGCP6, a core component of the γ-tubulin ring complex (γ-TuRC) that is
required for the nucleation of centriolar microtubules
explanation: >-
Identifies TUBGCP6 as a core γ-TuRC component in the cell-biology study;
it does not test a patient allele or a developmental disease model.
downstream:
- target: Reduced Centrosome-Driven Microtubule Nucleation
causal_link_type: DIRECT
description: >-
Acute loss of TUBGCP6 reduced centrosome-driven microtubule nucleation in
DLD-1 cells. Application to germline patient alleles is model extrapolation.
evidence:
- reference: PMID:31874114
reference_title: WBP11 is required for splicing the TUBGCP6 pre-mRNA to promote centriole duplication.
supports: SUPPORT
evidence_source: IN_VITRO
snippet: >-
Cells depleted of TUBGCP6 also exhibited mitotic defects similar to those
observed following loss of WBP11, including reduced centrosome-driven
microtubule nucleation and mitotic arrest with a monopolar spindle (Fig.
2, G and H; Fig. 7, E–G; and Videos 5 and 6).
explanation: >-
Directly measures reduced nucleation after acute TUBGCP6 depletion in
DLD-1 cells; it does not test a patient allele.
- target: Centriole Duplication Failure
causal_link_type: DIRECT
description: >-
Acute endogenous TUBGCP6 degradation caused centriole-duplication failure
in DLD-1 cells, and a TUBGCP6 transgene rescued that experimental defect.
evidence:
- reference: PMID:31874114
reference_title: WBP11 is required for splicing the TUBGCP6 pre-mRNA to promote centriole duplication.
supports: SUPPORT
evidence_source: IN_VITRO
snippet: >-
Degradation of TUBGCP6 led to a pronounced failure of centriole
duplication that was similar to that observed in WBP11AID cells (Fig. 7,
A–C).
explanation: >-
Directly demonstrates the cellular consequence of acute TUBGCP6 loss,
with the caveat that this is not a patient-allele experiment.
- name: Reduced Centrosome-Driven Microtubule Nucleation
biological_scale: CELLULAR
description: >-
Acute degradation of endogenously tagged TUBGCP6 in DLD-1 cells reduced
centrosome-driven microtubule nucleation. This is a direct cellular assay in
a colon-cancer cell line; neither neural nor retinal progenitors were tested.
biological_processes:
- preferred_term: microtubule nucleation
term:
id: GO:0007020
label: microtubule nucleation
modifier: DECREASED
evidence:
- reference: PMID:31874114
reference_title: WBP11 is required for splicing the TUBGCP6 pre-mRNA to promote centriole duplication.
supports: SUPPORT
evidence_source: IN_VITRO
snippet: >-
Cells depleted of TUBGCP6 also exhibited mitotic defects similar to those
observed following loss of WBP11, including reduced centrosome-driven
microtubule nucleation and mitotic arrest with a monopolar spindle (Fig. 2,
G and H; Fig. 7, E–G; and Videos 5 and 6).
explanation: Directly reports reduced centrosome-driven microtubule nucleation.
downstream:
- target: Monopolar-Spindle Mitotic Arrest
causal_link_type: UNKNOWN
description: >-
Reduced nucleation and monopolar-spindle arrest co-occurred after the same
depletion; the experiment did not isolate nucleation as the sole mediator.
evidence:
- reference: PMID:31874114
reference_title: WBP11 is required for splicing the TUBGCP6 pre-mRNA to promote centriole duplication.
supports: SUPPORT
evidence_source: IN_VITRO
snippet: >-
Cells depleted of TUBGCP6 also exhibited mitotic defects similar to those
observed following loss of WBP11, including reduced centrosome-driven
microtubule nucleation and mitotic arrest with a monopolar spindle (Fig.
2, G and H; Fig. 7, E–G; and Videos 5 and 6).
explanation: >-
Shows co-occurrence under one perturbation but does not establish that
reduced nucleation alone causes the arrest.
- name: Centriole Duplication Failure
biological_scale: CELLULAR
description: >-
Acute degradation of both endogenously tagged TUBGCP6 alleles in DLD-1 cells
produced a pronounced failure of centriole duplication. Rescue by a TUBGCP6
transgene supports perturbation specificity, but this remains an acute
cell-line model rather than a germline patient-allele assay.
biological_processes:
- preferred_term: centriole replication
term:
id: GO:0007099
label: centriole replication
modifier: DECREASED
evidence:
- reference: PMID:31874114
reference_title: WBP11 is required for splicing the TUBGCP6 pre-mRNA to promote centriole duplication.
supports: SUPPORT
evidence_source: IN_VITRO
snippet: >-
Degradation of TUBGCP6 led to a pronounced failure of centriole
duplication that was similar to that observed in WBP11AID cells (Fig. 7,
A–C).
explanation: Directly reports centriole-duplication failure after TUBGCP6 loss.
- reference: PMID:31874114
reference_title: WBP11 is required for splicing the TUBGCP6 pre-mRNA to promote centriole duplication.
supports: SUPPORT
evidence_source: IN_VITRO
snippet: >-
Expression of a TUBGCP6 transgene fully rescued centriole duplication in
auxin-treated TUBGCP6AID cells, demonstrating that this transgene was able
to functionally compensate for the loss of the endogenous protein (Fig.
S5, F and G).
explanation: Rescue supports specificity of the acute TUBGCP6-depletion phenotype.
downstream:
- target: Monopolar-Spindle Mitotic Arrest
causal_link_type: UNKNOWN
description: >-
Centriole-duplication failure and monopolar-spindle arrest co-occurred after
TUBGCP6 depletion, but the paper did not isolate their causal ordering.
evidence:
- reference: PMID:31874114
reference_title: WBP11 is required for splicing the TUBGCP6 pre-mRNA to promote centriole duplication.
supports: SUPPORT
evidence_source: IN_VITRO
snippet: >-
First, loss of TUBGCP6, WBP11, and SNW1 share phenotypic similarities,
including the formation of monopolar spindles, a prolonged mitosis, and
centriole duplication failure.
explanation: >-
Reports both phenotypes after loss of TUBGCP6 but does not resolve the
ordering between duplication failure and monopolar arrest.
- name: Monopolar-Spindle Mitotic Arrest
biological_scale: CELLULAR
description: >-
TUBGCP6-depleted DLD-1 cells developed mitotic arrest with a monopolar
spindle and predominantly underwent mitotic slippage at later observation
times. These are in-vitro cell-division phenotypes.
biological_processes:
- preferred_term: mitotic spindle organization
term:
id: GO:0007052
label: mitotic spindle organization
modifier: DYSREGULATED
evidence:
- reference: PMID:31874114
reference_title: WBP11 is required for splicing the TUBGCP6 pre-mRNA to promote centriole duplication.
supports: SUPPORT
evidence_source: IN_VITRO
snippet: >-
Cells depleted of TUBGCP6 also exhibited mitotic defects similar to those
observed following loss of WBP11, including reduced centrosome-driven
microtubule nucleation and mitotic arrest with a monopolar spindle (Fig. 2,
G and H; Fig. 7, E–G; and Videos 5 and 6).
explanation: Directly reports the monopolar-spindle mitotic arrest phenotype.
downstream:
- target: Reduced Cell Proliferation
causal_link_type: DIRECT
description: The mitotic deficits reduced proliferation in the same cell model.
evidence:
- reference: PMID:31874114
reference_title: WBP11 is required for splicing the TUBGCP6 pre-mRNA to promote centriole duplication.
supports: SUPPORT
evidence_source: IN_VITRO
snippet: >-
Similar to WBP11AID cells, the mitotic deficits dramatically reduced the
proliferation of cells depleted of TUBGCP6 (Fig. 7 H).
explanation: Directly links the observed mitotic deficits to reduced proliferation.
- name: Reduced Cell Proliferation
biological_scale: CELLULAR
description: >-
Acute TUBGCP6 depletion dramatically reduced proliferation of DLD-1 cells.
Reduced developmental progenitor output is a plausible bridge to the brain,
chorioretinal, and somatic-growth endpoints, but that bridge has not been
tested in patient-derived, neural, or retinal models.
biological_processes:
- preferred_term: cell population proliferation
term:
id: GO:0008283
label: cell population proliferation
modifier: DECREASED
evidence:
- reference: PMID:31874114
reference_title: WBP11 is required for splicing the TUBGCP6 pre-mRNA to promote centriole duplication.
supports: SUPPORT
evidence_source: IN_VITRO
snippet: >-
Similar to WBP11AID cells, the mitotic deficits dramatically reduced the
proliferation of cells depleted of TUBGCP6 (Fig. 7 H).
explanation: Directly reports reduced proliferation in TUBGCP6-depleted cells.
downstream:
- target: Abnormal Cerebral Development
causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
intermediate_mechanisms:
- Developmental neural-progenitor loss or dysfunction is hypothesized but untested in TUBGCP6 models.
description: >-
The cellular model and human cerebral phenotype are consistent with this
bridge, but no TUBGCP6 neural-development experiment establishes it.
evidence:
- reference: PMID:22279524
reference_title: Genetic mapping and exome sequencing identify variants associated with five novel diseases.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Magnetic resonance imaging shows diffuse pachygyria (Figure 2, C). The
cerebral hemispheres are small relative to the cerebellum, which has a
hypoplastic vermis (Figure 2, D).
explanation: >-
Establishes the human cerebral endpoint but not the mechanistic bridge
from the DLD-1 proliferation assay.
- target: Abnormal Chorioretinal Development
causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
intermediate_mechanisms:
- Developmental retinal or choroidal progenitor loss or dysfunction is hypothesized but untested in TUBGCP6 models.
description: >-
The cellular model and human chorioretinal phenotype are consistent with
this bridge, but no TUBGCP6 retinal-development experiment establishes it.
evidence:
- reference: PMID:22279524
reference_title: Genetic mapping and exome sequencing identify variants associated with five novel diseases.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The retina and choroid are underdeveloped and have focal defects that
reveal bare sclera.
explanation: >-
Establishes the human tissue endpoint but not the mechanistic bridge
from the DLD-1 proliferation assay.
- target: Reduced Somatic Growth
causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
intermediate_mechanisms:
- Developmental growth restriction downstream of impaired proliferation is hypothesized but untested for patient alleles.
description: >-
Short stature is reported clinically, but the cellular-to-organism growth
bridge has not been tested for TUBGCP6 patient variants.
evidence:
- reference: PMID:39634241
reference_title: Two-Compound Heterozygous Deletions Affecting TUBGCP6 in a Patient with Microcephaly and Ocular Abnormalities and in an Unborn Sibling with Abnormal Sulcation.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
We present the first Indian family with an affected child and sibling
fetus with microcephaly, dysmorphism, and agyria/pachygyria complex on
brain imaging in both and short stature, intellectual disability, and
visual impairment in proband.
explanation: Reports the human growth endpoint without establishing its cellular mechanism.
- name: Abnormal Cerebral Development
biological_scale: TISSUE
description: >-
Human findings include congenital severe microcephaly, diffuse pachygyria,
small cerebral hemispheres, cerebellar vermis hypoplasia, developmental and
intellectual impairment, and occasional seizures. Later reports extend the
imaging spectrum to agyria/pachygyria, ventriculomegaly, and abnormal
sulcation. These observations define the tissue endpoint rather than proving
the upstream cellular bridge.
evidence:
- reference: PMID:22279524
reference_title: Genetic mapping and exome sequencing identify variants associated with five novel diseases.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Magnetic resonance imaging shows diffuse pachygyria (Figure 2, C). The
cerebral hemispheres are small relative to the cerebellum, which has a
hypoplastic vermis (Figure 2, D).
explanation: Directly documents the cerebral malformation pattern in the original cohort.
- reference: PMID:39634241
reference_title: Two-Compound Heterozygous Deletions Affecting TUBGCP6 in a Patient with Microcephaly and Ocular Abnormalities and in an Unborn Sibling with Abnormal Sulcation.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
We report third trimester microcephaly with ventriculomegaly and abnormal
sulcation as part of the antenatal presentation for this condition.
explanation: Extends the prenatal cerebral-imaging spectrum in one family.
downstream:
- target: Microcephaly
causal_link_type: DIRECT
description: Reduced cerebral growth presents as congenital microcephaly.
evidence:
- reference: PMID:22279524
reference_title: Genetic mapping and exome sequencing identify variants associated with five novel diseases.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
All patients are born with microcephaly, a sloping forehead, diminutive
anterior fontanelle, and sutural ridging (Figure 2, A).
explanation: Directly documents congenital microcephaly in the original cohort.
- target: Global Developmental Delay
causal_link_type: DIRECT
description: Developmental delay is part of the reported cerebral phenotype.
evidence:
- reference: PMID:22279524
reference_title: Genetic mapping and exome sequencing identify variants associated with five novel diseases.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Children walk independently between 14 and 36 months of age and language
emerges at an appropriate age but remains rudimentary.
explanation: Documents delayed walking and limited language development.
- target: Intellectual Disability
causal_link_type: DIRECT
description: Intellectual impairment accompanies the congenital brain phenotype.
evidence:
- reference: PMID:37031378
reference_title: "Biallelic variants in TUBGCP6 result in microcephaly and chorioretinopathy 1: Report of four cases and a literature review."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Clinical features of this disorder include microcephaly, cognitive
impairment, dysmorphic features, and variable ophthalmological anomalies
including chorioretinopathy.
explanation: Lists cognitive impairment among the clinical features.
- target: Pachygyria
causal_link_type: DIRECT
description: Pachygyria is a directly imaged cortical malformation.
evidence:
- reference: PMID:22279524
reference_title: Genetic mapping and exome sequencing identify variants associated with five novel diseases.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: Magnetic resonance imaging shows diffuse pachygyria (Figure 2, C).
explanation: Directly reports diffuse pachygyria on MRI.
- target: Hypoplasia of the Corpus Callosum
causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
description: >-
At this tissue-to-phenotype graph scale, reduced callosal area is an
observed structural manifestation of abnormal cerebral development. This
does not establish the upstream cellular mechanism or a disease-wide
frequency.
evidence:
- reference: PMID:22279524
reference_title: Genetic mapping and exome sequencing identify variants associated with five novel diseases.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: |-
area of the corpus callosum is approximately half that of an age-
matched control child (2.75 cm 2 versus 5.61 cm 2).
explanation: >-
Quantifies reduced corpus-callosum area in one imaged child; the HPO
hypoplasia mapping is a conservative anatomical interpretation.
- target: Cerebellar Vermis Hypoplasia
causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
description: >-
A hypoplastic vermis is a directly imaged structural manifestation at the
cerebral-development tissue endpoint.
evidence:
- reference: PMID:22279524
reference_title: Genetic mapping and exome sequencing identify variants associated with five novel diseases.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The cerebral hemispheres are small relative to the cerebellum, which has
a hypoplastic vermis (Figure 2, D).
explanation: Directly documents cerebellar vermis hypoplasia on MRI.
- target: Seizure
causal_link_type: DIRECT
description: Seizures occurred in a minority of the original cohort.
evidence:
- reference: PMID:22279524
reference_title: Genetic mapping and exome sequencing identify variants associated with five novel diseases.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Two of nine patients (22%) have epilepsy: one started having drop attacks
in late childhood and another developed nocturnal epilepsy as an adult.
explanation: Provides the exact cohort-specific seizure count and presentations.
- name: Abnormal Chorioretinal Development
biological_scale: TISSUE
description: >-
The original cohort had underdeveloped retina and choroid with focal areas of
bare sclera, scalloped retina, abnormal peripheral tissue, vitreoretinal
traction, and risk of retinal detachment. This anatomy is better represented
by broad abnormal chorioretinal morphology than by assuming a uniform
progressive dystrophy.
evidence:
- reference: PMID:22279524
reference_title: Genetic mapping and exome sequencing identify variants associated with five novel diseases.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The retina and choroid are underdeveloped and have focal defects that
reveal bare sclera.
explanation: Directly describes abnormal chorioretinal development.
downstream:
- target: Chorioretinopathy
causal_link_type: DIRECT
description: Underdeveloped retina and choroid produce the defining ocular morphology.
evidence:
- reference: PMID:22279524
reference_title: Genetic mapping and exome sequencing identify variants associated with five novel diseases.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The retina and choroid are underdeveloped and have focal defects that
reveal bare sclera.
explanation: Directly supports abnormal chorioretinal morphology.
- target: Visual Impairment
causal_link_type: DIRECT
description: The ocular abnormality is accompanied by early visual impairment.
evidence:
- reference: PMID:37031378
reference_title: "Biallelic variants in TUBGCP6 result in microcephaly and chorioretinopathy 1: Report of four cases and a literature review."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Microcephaly can be recognized prenatally and visual impairment becomes
evident during the first year of life.
explanation: Directly reports visual impairment and its observed onset.
- target: Retinal Detachment
causal_link_type: DIRECT
description: Vitreoretinal traction creates points at risk for retinal detachment.
evidence:
- reference: PMID:22279524
reference_title: Genetic mapping and exome sequencing identify variants associated with five novel diseases.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Condensations of vitreous may attach to the retina in transition regions
between scalloped and gray tissue, marking points of traction for retinal
detachment.
explanation: Directly describes the tractional basis for retinal detachment.
- name: Reduced Somatic Growth
biological_scale: ORGANISM
description: >-
Short stature is reported in TUBGCP6-affected individuals, including the
proband with compound-heterozygous deletion alleles. The relationship to the
DLD-1 proliferation phenotype is plausible but untested.
evidence:
- reference: PMID:39634241
reference_title: Two-Compound Heterozygous Deletions Affecting TUBGCP6 in a Patient with Microcephaly and Ocular Abnormalities and in an Unborn Sibling with Abnormal Sulcation.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
We present the first Indian family with an affected child and sibling
fetus with microcephaly, dysmorphism, and agyria/pachygyria complex on brain
imaging in both and short stature, intellectual disability, and visual
impairment in proband.
explanation: Directly reports short stature in the affected proband.
- reference: PMID:25344692
reference_title: Mutations in PLK4, encoding a master regulator of centriole biogenesis, cause microcephaly, growth failure and retinopathy.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Here we identify mutations in the genes encoding PLK4 kinase, a master
regulator of centriole duplication, and its substrate TUBGCP6 in
individuals with microcephalic primordial dwarfism and additional
congenital anomalies, including retinopathy, thereby extending the human
phenotypic spectrum associated with centriole dysfunction.
explanation: >-
Supports growth restriction in the combined PLK4/TUBGCP6 ascertainment;
the source abstract does not separate gene-specific counts.
downstream:
- target: Short Stature
causal_link_type: DIRECT
description: Reduced somatic growth is clinically expressed as short stature.
evidence:
- reference: PMID:39634241
reference_title: Two-Compound Heterozygous Deletions Affecting TUBGCP6 in a Patient with Microcephaly and Ocular Abnormalities and in an Unborn Sibling with Abnormal Sulcation.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
We present the first Indian family with an affected child and sibling
fetus with microcephaly, dysmorphism, and agyria/pachygyria complex on
brain imaging in both and short stature, intellectual disability, and
visual impairment in proband.
explanation: Directly reports short stature in the proband.
phenotypes:
- name: Microcephaly
description: >-
Congenital microcephaly was severe in the original cohort and has also been
recognized prenatally in later families.
phenotype_term:
preferred_term: Microcephaly
term:
id: HP:0000252
label: Microcephaly
evidence:
- reference: PMID:22279524
reference_title: Genetic mapping and exome sequencing identify variants associated with five novel diseases.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
All patients are born with microcephaly, a sloping forehead, diminutive
anterior fontanelle, and sutural ridging (Figure 2, A).
explanation: Directly documents congenital microcephaly in the original cohort.
- name: Sloping Forehead
description: >-
Sloping forehead accompanied congenital microcephaly in the founding cohort.
It is retained as an unwired clinical phenotype because the source reports
co-occurrence but does not establish a directional cerebral-development
mechanism.
phenotype_term:
preferred_term: Sloping forehead
term:
id: HP:0000340
label: Sloping forehead
evidence:
- reference: PMID:22279524
reference_title: Genetic mapping and exome sequencing identify variants associated with five novel diseases.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
All patients are born with microcephaly, a sloping forehead, diminutive
anterior fontanelle, and sutural ridging (Figure 2, A).
explanation: Directly reports sloping forehead in the founding cohort.
- name: Chorioretinopathy
description: >-
Variable abnormal chorioretinal morphology, including underdevelopment and
focal defects of the retina and choroid. The broad HPO term is intentional:
the later disease review describes variable ophthalmological anomalies, and
the founding cohort's developmental morphology does not establish uniform
formal dysplasia or progressive dystrophy across all affected individuals.
phenotype_term:
preferred_term: Abnormal chorioretinal morphology
term:
id: HP:0000532
label: Abnormal chorioretinal morphology
evidence:
- reference: PMID:22279524
reference_title: Genetic mapping and exome sequencing identify variants associated with five novel diseases.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The retina and choroid are underdeveloped and have focal defects that
reveal bare sclera.
explanation: Directly describes the chorioretinal morphology.
- name: Visual Impairment
description: Visual impairment may become evident during the first year of life.
phenotype_term:
preferred_term: Visual impairment
term:
id: HP:0000505
label: Visual impairment
evidence:
- reference: PMID:37031378
reference_title: "Biallelic variants in TUBGCP6 result in microcephaly and chorioretinopathy 1: Report of four cases and a literature review."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: visual impairment becomes evident during the first year of life
explanation: Directly reports early visual impairment.
- name: Intellectual Disability
description: Intellectual or cognitive impairment is part of the reported phenotype.
phenotype_term:
preferred_term: Intellectual disability
term:
id: HP:0001249
label: Intellectual disability
evidence:
- reference: PMID:39634241
reference_title: Two-Compound Heterozygous Deletions Affecting TUBGCP6 in a Patient with Microcephaly and Ocular Abnormalities and in an Unborn Sibling with Abnormal Sulcation.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
We present the first Indian family with an affected child and sibling fetus
with microcephaly, dysmorphism, and agyria/pachygyria complex on brain
imaging in both and short stature, intellectual disability, and visual
impairment in proband.
explanation: Directly reports intellectual disability in the affected proband.
- name: Global Developmental Delay
description: Delayed independent walking and limited language were described in the original cohort.
phenotype_term:
preferred_term: Global developmental delay
term:
id: HP:0001263
label: Global developmental delay
evidence:
- reference: PMID:22279524
reference_title: Genetic mapping and exome sequencing identify variants associated with five novel diseases.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Children walk independently between 14 and 36 months of age and language
emerges at an appropriate age but remains rudimentary.
explanation: Documents delayed walking and limited language development.
- name: Pachygyria
description: Diffuse pachygyria is reported on MRI; a later family had an agyria/pachygyria complex.
phenotype_term:
preferred_term: Pachygyria
term:
id: HP:0001302
label: Pachygyria
evidence:
- reference: PMID:22279524
reference_title: Genetic mapping and exome sequencing identify variants associated with five novel diseases.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: Magnetic resonance imaging shows diffuse pachygyria (Figure 2, C).
explanation: Directly reports diffuse pachygyria on MRI.
- name: Hypoplasia of the Corpus Callosum
description: >-
One imaged affected child had a corpus-callosum surface area approximately
half that of an age-matched control. The phenotype is recorded without a
disease-wide frequency, and the HPO hypoplasia mapping is conservative
because the source reports the quantitative reduction rather than naming it.
phenotype_term:
preferred_term: Hypoplasia of the corpus callosum
term:
id: HP:0002079
label: Hypoplasia of the corpus callosum
evidence:
- reference: PMID:22279524
reference_title: Genetic mapping and exome sequencing identify variants associated with five novel diseases.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: |-
area of the corpus callosum is approximately half that of an age-
matched control child (2.75 cm 2 versus 5.61 cm 2).
explanation: >-
Supports reduced callosal size in one child; the hypoplasia term is an
anatomical interpretation rather than source wording.
- name: Cerebellar Vermis Hypoplasia
description: >-
A hypoplastic cerebellar vermis accompanied the small cerebral hemispheres
on MRI. This phenotype assertion is retained separately from the structured
imaging finding because the schema serves both clinical-phenotype and
imaging consumers.
phenotype_term:
preferred_term: Cerebellar vermis hypoplasia
term:
id: HP:0001320
label: Cerebellar vermis hypoplasia
evidence:
- reference: PMID:22279524
reference_title: Genetic mapping and exome sequencing identify variants associated with five novel diseases.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The cerebral hemispheres are small relative to the cerebellum, which has a
hypoplastic vermis (Figure 2, D).
explanation: Directly reports cerebellar vermis hypoplasia on MRI.
- name: Short Stature
description: Short stature is reported in the proband from the deletion-allele family.
phenotype_term:
preferred_term: Short stature
term:
id: HP:0004322
label: Short stature
evidence:
- reference: PMID:39634241
reference_title: Two-Compound Heterozygous Deletions Affecting TUBGCP6 in a Patient with Microcephaly and Ocular Abnormalities and in an Unborn Sibling with Abnormal Sulcation.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
We present the first Indian family with an affected child and sibling fetus
with microcephaly, dysmorphism, and agyria/pachygyria complex on brain
imaging in both and short stature, intellectual disability, and visual
impairment in proband.
explanation: Directly reports short stature in the affected proband.
- name: Seizure
description: >-
Seizures were reported in two of nine people in the original Mennonite
cohort; this cohort-specific observation should not be generalized into a
disease-wide prevalence estimate.
frequency: 2/9 (22%) in the original Mennonite cohort
phenotype_term:
preferred_term: Seizure
term:
id: HP:0001250
label: Seizure
evidence:
- reference: PMID:22279524
reference_title: Genetic mapping and exome sequencing identify variants associated with five novel diseases.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Two of nine patients (22%) have epilepsy: one started having drop attacks
in late childhood and another developed nocturnal epilepsy as an adult.
explanation: Gives the exact cohort-specific count and seizure presentations.
- name: Retinal Detachment
description: >-
Vitreoretinal condensations and traction were described at transition zones,
providing a structural basis for retinal detachment.
phenotype_term:
preferred_term: Retinal detachment
term:
id: HP:0000541
label: Retinal detachment
evidence:
- reference: PMID:22279524
reference_title: Genetic mapping and exome sequencing identify variants associated with five novel diseases.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Condensations of vitreous may attach to the retina in transition regions
between scalloped and gray tissue, marking points of traction for retinal
detachment.
explanation: Directly describes traction associated with retinal detachment.
genetic:
- name: TUBGCP6
association: Causative
gene_term:
preferred_term: TUBGCP6 (tubulin gamma complex associated protein 6)
term:
id: hgnc:18127
label: TUBGCP6
notes: >-
TUBGCP6 encodes a gamma-tubulin-complex associated protein, not a tubulin
isotype. MCCRP1 is kept distinct from TUBGCP4-, TUBGCP2-, TUBG1-, KIF11-,
and PLK4-related disorders despite mechanistic or phenotypic overlap.
evidence:
- reference: PMID:37031378
reference_title: "Biallelic variants in TUBGCP6 result in microcephaly and chorioretinopathy 1: Report of four cases and a literature review."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
biallelic loss of function variants in Tubulin-Gamma Complex Associated
Protein 6 (TUBGCP6, MIM#610053)
explanation: Names TUBGCP6 as the biallelic causative gene.
epidemiology:
- name: Molecularly confirmed cases reported before the 2023 series
description: >-
The 2023 review stated that seven molecularly confirmed patients from five
unrelated families had previously been reported. This is a literature case
count, not a population prevalence estimate.
evidence:
- reference: PMID:37031378
reference_title: "Biallelic variants in TUBGCP6 result in microcephaly and chorioretinopathy 1: Report of four cases and a literature review."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
To date, only seven molecularly confirmed patients from five unrelated
families have been reported.
explanation: Gives the source-specific pre-existing case and family count.
- name: Cases added by the 2023 series
description: >-
The 2023 report added four unrelated patients, including one prenatal
diagnosis. This report-specific increment is kept separate from the prior
case count to avoid an inferred pooled denominator.
evidence:
- reference: PMID:37031378
reference_title: "Biallelic variants in TUBGCP6 result in microcephaly and chorioretinopathy 1: Report of four cases and a literature review."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
We report an additional four unrelated patients with TUBGCP6 variants
including one prenatal diagnosis and review the clinical phenotypes and
genotypes of all the known cases.
explanation: Gives the report-specific increment and prenatal case.
diagnosis:
- name: Ophthalmological examination
description: >-
Ophthalmological assessment can characterize the retina, choroid, and
vitreoretinal interface. The original description documents underdevelopment,
focal defects, and traction associated with detachment rather than one uniform
dystrophic pattern.
diagnosis_term:
preferred_term: eye examination
term:
id: NCIT:C38060
label: Eye Examination
evidence:
- reference: PMID:22279524
reference_title: Genetic mapping and exome sequencing identify variants associated with five novel diseases.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The retina and choroid are underdeveloped and have focal defects that
reveal bare sclera.
explanation: Documents the ocular anatomy that ophthalmological evaluation must characterize.
- name: Sequence and structural-variant-sensitive genetic testing
description: >-
Confirmation requires two pathogenic TUBGCP6 alleles. Testing should be able
to detect small sequence variants and deletions or other structural variants;
genome sequencing identified an 11-base-pair deletion in trans with a
405-base-pair deletion in one family.
diagnosis_term:
preferred_term: genetic testing
term:
id: NCIT:C15709
label: Genetic Testing
evidence:
- reference: PMID:39634241
reference_title: Two-Compound Heterozygous Deletions Affecting TUBGCP6 in a Patient with Microcephaly and Ocular Abnormalities and in an Unborn Sibling with Abnormal Sulcation.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Genome sequencing through the Indian Undiagnosed Disease Program (I-UDP)
confirmed the diagnosis in both proband and sibling fetus. Compound
heterozygous variants were identified in TUBGCP6 including an eleven base
pair deletion (inherited from father) and 405 base pair large deletion
(inherited from mother).
explanation: >-
Directly supports genome sequencing and deletion-sensitive analysis for
molecular confirmation.
treatments:
- name: Genetic Counseling
description: >-
Establishing the biallelic TUBGCP6 diagnosis can inform family reproductive
planning. The cited source supports that management consequence but does not
state a numeric recurrence risk, surveillance schedule, or treatment outcome,
so none is asserted here.
treatment_term:
preferred_term: Genetic Counseling
term:
id: NCIT:C15240
label: Genetic Counseling
evidence:
- reference: PMID:37031378
reference_title: "Biallelic variants in TUBGCP6 result in microcephaly and chorioretinopathy 1: Report of four cases and a literature review."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
it is important to recognize and diagnose this syndrome in view of its
impact on patient health management and familial reproductive plans
explanation: >-
Supports reproductive-planning implications of molecular recognition;
it does not provide a counseling protocol or a numeric recurrence figure.
imaging_findings:
- name: Diffuse pachygyria on brain MRI
modality: MRI
imaging_finding_term:
preferred_term: Pachygyria
term:
id: HP:0001302
label: Pachygyria
located_in:
preferred_term: brain
term:
id: UBERON:0000955
label: brain
spatial_extent: DIFFUSE
diagnostic: false
description: Diffuse pachygyria was documented by MRI in the original cohort.
evidence:
- reference: PMID:22279524
reference_title: Genetic mapping and exome sequencing identify variants associated with five novel diseases.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Microcephaly with chorioretinopathy. The phenotype was originally described by Victor McKusick
... Magnetic resonance imaging shows diffuse pachygyria (Figure 2, C). ... Microcephaly and
chorioretinopathy due to a homozygous TUBGCP6 mutation.
explanation: >-
Retains the diffuse-pachygyria observation and restores the microcephaly/chorioretinopathy
context and the figure's explicit TUBGCP6 attribution. Ellipses mark omitted source text in
order.
- name: Cerebellar vermis hypoplasia on brain MRI
modality: MRI
imaging_finding_term:
preferred_term: Cerebellar vermis hypoplasia
term:
id: HP:0001320
label: Cerebellar vermis hypoplasia
located_in:
preferred_term: cerebellar vermis
term:
id: UBERON:0004720
label: cerebellar vermis
diagnostic: false
description: A hypoplastic cerebellar vermis accompanied small cerebral hemispheres on MRI.
evidence:
- reference: PMID:22279524
reference_title: Genetic mapping and exome sequencing identify variants associated with five novel diseases.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The cerebral hemispheres are small relative to the cerebellum, which has a
hypoplastic vermis (Figure 2, D).
explanation: Directly reports cerebellar vermis hypoplasia on MRI.
- name: Prenatal ventriculomegaly and abnormal sulcation on fetal imaging
modality: OTHER
imaging_finding_term:
preferred_term: Ventriculomegaly
term:
id: HP:0002119
label: Ventriculomegaly
located_in:
preferred_term: brain
term:
id: UBERON:0000955
label: brain
diagnostic: false
description: >-
Ventriculomegaly and abnormal sulcation were reported in the third trimester.
The cached abstract does not identify the imaging modality, so OTHER is used
rather than inferring ultrasound or MRI.
evidence:
- reference: PMID:39634241
reference_title: Two-Compound Heterozygous Deletions Affecting TUBGCP6 in a Patient with Microcephaly and Ocular Abnormalities and in an Unborn Sibling with Abnormal Sulcation.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
We report third trimester microcephaly with ventriculomegaly and abnormal
sulcation as part of the antenatal presentation for this condition.
explanation: Directly reports the prenatal findings without specifying modality.
differential_diagnoses:
- name: Congenital toxoplasmosis or cytomegalovirus infection
description: >-
Acquired congenital infection can combine microcephaly with chorioretinal
abnormalities. Infection testing and demonstration of biallelic TUBGCP6
variants distinguish these acquired conditions from MCCRP1.
distinguishing_features:
- MCCRP1 is confirmed by biallelic TUBGCP6 variants.
evidence:
- reference: PMID:37031378
reference_title: "Biallelic variants in TUBGCP6 result in microcephaly and chorioretinopathy 1: Report of four cases and a literature review."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The clinical presentation resembles the findings in some acquired
conditions such as congenital toxoplasmosis and cytomegalovirus infections;
thus, it is important to recognize and diagnose this syndrome in view of
its impact on patient health management and familial reproductive plans.
explanation: Directly identifies the acquired-infection differential.
- name: KIF11-related microcephaly with chorioretinal dysplasia
description: >-
KIF11-related disease overlaps through microcephaly, chorioretinal dysplasia,
retinal folds or detachment, and a FEVR-like presentation. Heterozygous KIF11
variants and possible lymphedema distinguish it from recessive TUBGCP6 MCCRP1.
distinguishing_features:
- KIF11-related disease is associated with heterozygous KIF11 variants.
- Lymphedema and FEVR-like peripheral avascularity favor KIF11-related disease.
evidence:
- reference: PMID:25124931
reference_title: Phenotypic overlap between familial exudative vitreoretinopathy and microcephaly, lymphedema, and chorioretinal dysplasia caused by KIF11 mutations.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Retinal detachment with avascularity of the peripheral retina, typically
associated with familial exudative vitreoretinopathy (FEVR), can result
from mutations in KIF11, a gene recently identified to cause microcephaly,
lymphedema, and chorioretinal dysplasia (MLCRD) as well as chorioretinal
dysplasia, microcephaly, and mental retardation (CDMMR).
explanation: Defines the overlapping KIF11-associated neuro-ophthalmic phenotype.
- reference: PMID:25124931
reference_title: Phenotypic overlap between familial exudative vitreoretinopathy and microcephaly, lymphedema, and chorioretinal dysplasia caused by KIF11 mutations.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Four novel heterozygous KIF11 mutations and 1 previously published mutation
were identified in probands with FEVR: p.A218Gfs*15, p.E470X, p.R221G,
c.790-1G>T, and the previously described heterozygous p.R47X. Documentation
of peripheral avascular areas on intravenous fluorescein angiography was
possible in 2 probands with fibrovascular proliferation demonstrating
phenotypic overlap with FEVR.
explanation: Supports the heterozygous KIF11 and peripheral-avascularity distinctions.
- name: TUBGCP4-related microcephaly and chorioretinopathy
description: >-
TUBGCP4-related disease is a distinct autosomal-recessive
gamma-tubulin-complex disorder with overlapping microcephaly and
chorioretinopathy. Molecular identification of TUBGCP4 rather than TUBGCP6
variants distinguishes it.
distinguishing_features:
- Causative biallelic variants are in TUBGCP4 rather than TUBGCP6.
- Patient-fibroblast functional findings reported for TUBGCP4 must not be transferred to TUBGCP6.
evidence:
- reference: PMID:25817018
reference_title: Mutations in TUBGCP4 alter microtubule organization via the γ-tubulin ring complex in autosomal-recessive microcephaly with chorioretinopathy.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
We have identified TUBGCP4 variants in individuals with autosomal-recessive
microcephaly and chorioretinopathy. Whole-exome sequencing performed on one
family with two affected siblings and independently on another family with
one affected child revealed compound-heterozygous mutations in TUBGCP4.
explanation: Directly defines the overlapping but genetically distinct TUBGCP4 disorder.
- name: PLK4-related microcephalic primordial dwarfism
description: >-
PLK4-related disease overlaps through severe microcephaly, growth failure,
retinopathy, and additional congenital anomalies. Molecular identification
of PLK4 rather than TUBGCP6 variants establishes the distinct diagnosis; PLK4
cell and zebrafish experiments do not provide TUBGCP6 functional evidence.
distinguishing_features:
- Causative variants are in PLK4 rather than TUBGCP6.
evidence:
- reference: PMID:25344692
reference_title: Mutations in PLK4, encoding a master regulator of centriole biogenesis, cause microcephaly, growth failure and retinopathy.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Here we identify mutations in the genes encoding PLK4 kinase, a master
regulator of centriole duplication, and its substrate TUBGCP6 in
individuals with microcephalic primordial dwarfism and additional
congenital anomalies, including retinopathy, thereby extending the human
phenotypic spectrum associated with centriole dysfunction.
explanation: Establishes the overlapping PLK4 and TUBGCP6 clinical ascertainment.
discussions:
- discussion_id: gap_tubgcp6_patient_allele_and_developmental_models
prompt: >-
Do biallelic patient alleles reproduce the acute TUBGCP6-depletion phenotype
in neural and retinal developmental systems, and which cellular defect
drives each organ phenotype?
kind: KNOWLEDGE_GAP
status: OPEN
attaches_to:
- pathophysiology#Reduced TUBGCP6 Function
- pathophysiology#Reduced Cell Proliferation
- pathophysiology#Abnormal Cerebral Development
- pathophysiology#Abnormal Chorioretinal Development
rationale: >-
Acute loss of endogenously tagged TUBGCP6 in DLD-1 cells has a specific,
rescuable effect on centriole duplication and also reduces nucleation and
proliferation. The model does not contain a disease allele and is neither
neural nor retinal. Human reports establish the brain and eye endpoints but
do not measure the intervening mechanism. Patient-derived cells, cerebral or
retinal organoids, and allele-specific rescue experiments are needed to test
the bridge and to distinguish effects of nucleation, centriole duplication,
mitotic arrest, and other unknown intermediates.
evidence:
- reference: PMID:31874114
reference_title: WBP11 is required for splicing the TUBGCP6 pre-mRNA to promote centriole duplication.
supports: SUPPORT
evidence_source: IN_VITRO
snippet: >-
Expression of a TUBGCP6 transgene fully rescued centriole duplication in
auxin-treated TUBGCP6AID cells, demonstrating that this transgene was able
to functionally compensate for the loss of the endogenous protein (Fig.
S5, F and G).
explanation: Establishes a specific rescuable cellular phenotype in the acute DLD-1 model.
- reference: PMID:37031378
reference_title: "Biallelic variants in TUBGCP6 result in microcephaly and chorioretinopathy 1: Report of four cases and a literature review."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Clinical features of this disorder include microcephaly, cognitive
impairment, dysmorphic features, and variable ophthalmological anomalies
including chorioretinopathy.
explanation: Establishes the human endpoints without testing the cellular bridge.
notes: >-
Reviewed against the original 2012 clinical report, later TUBGCP6 case series,
the 2024 deletion family, and a direct 2020 TUBGCP6-depletion study. MCCRP1 is
maintained as the MONDO:0009624 TUBGCP6 disorder and is not collapsed into
TUBGCP4-, TUBGCP2-, TUBG1-, KIF11-, PLK4-, or Seckel-spectrum diagnoses.

PMID:31874114 provides direct in-vitro evidence from acute degradation of both
endogenously tagged TUBGCP6 alleles in DLD-1 cells. It does not test germline
patient alleles, neural progenitors, retinal cells, or an animal model.
PMID:25344692 provides patient-level TUBGCP6 overlap in its abstract, but its
PLK4 cellular and zebrafish experiments are not transferred to TUBGCP6.
PMID:25817018 is used only to define the TUBGCP4 differential, not as evidence
for a TUBGCP6 mechanism.

The cached records for PMID:37031378 and PMID:39634241 expose abstract text for
snippet validation. PMID:22279524 and PMID:31874114 expose cached full text.
Genetic counseling is included only to the extent supported by the explicit
familial-reproductive-planning statement; no numeric recurrence risk is added.
No disease-specific treatment outcome, clinical trial, animal model, dataset,
or population prevalence was identified in the source-local review, so none
is asserted here.

📚

References & Deep Research

References

7

PMID:37031378

Biallelic variants in TUBGCP6 result in microcephaly and chorioretinopathy 1: Report of four cases and a literature review.

No top-level findings curated for this source.

PMID:39634241

Two-Compound Heterozygous Deletions Affecting TUBGCP6 in a Patient with Microcephaly and Ocular Abnormalities and in an Unborn Sibling with Abnormal Sulcation.

No top-level findings curated for this source.

PMID:22279524

Genetic mapping and exome sequencing identify variants associated with five novel diseases.

No top-level findings curated for this source.

PMID:25344692

Mutations in PLK4, encoding a master regulator of centriole biogenesis, cause microcephaly, growth failure and retinopathy.

No top-level findings curated for this source.

PMID:31874114

WBP11 is required for splicing the TUBGCP6 pre-mRNA to promote centriole duplication.

No top-level findings curated for this source.

PMID:25124931

Phenotypic overlap between familial exudative vitreoretinopathy and microcephaly, lymphedema, and chorioretinal dysplasia caused by KIF11 mutations.

No top-level findings curated for this source.

PMID:25817018

Mutations in TUBGCP4 alter microtubule organization via the γ-tubulin ring complex in autosomal-recessive microcephaly with chorioretinopathy.

No top-level findings curated for this source.

TUBGCP6-related Microcephaly and Chorioretinopathy

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References