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Malformations of cortical development v4.26 WNK3 Arina Puzriakova Phenotypes for gene: WNK3 were changed from Intellectual disability, MONDO:0001071 to Prieto syndrome, OMIM:309610; Intellectual disability, MONDO:0001071
Malformations of cortical development v4.25 WNK3 Arina Puzriakova Tag gene-checked was removed from gene: WNK3.
Malformations of cortical development v4.25 COL3A1 Eleanor Williams gene: COL3A1 was added
gene: COL3A1 was added to Malformations of cortical development. Sources: Literature
Mode of inheritance for gene: COL3A1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COL3A1 were set to 19455184; 25205403; 28742248; 28258187
Phenotypes for gene: COL3A1 were set to Polymicrogyria with or without vascular-type EDS, OMIM:618343; polymicrogyria with or without vascular-type Ehlers-Danlos syndrome, MONDO:0032688
Review for gene: COL3A1 was set to GREEN
Added comment: Associated with Polymicrogyria with or without vascular-type EDS in OMIM (OMIM:618343) with a autosomal recessive mode of inheritance.

Several cases reported:

PMID: 19455184 Plancke et al 2009 - report an 11 year old female with consangiuneous parents, who had vascular EDS. The phenotype also included diffuse cortical dysplasia. A homozygous nucleotide duplication (c.479dupT) in COL3A1 resulting in a premature termination codon (p.Lys161GlnfsX45) was identified. Both parents were heterozygous for this variant.

PMID: 25205403 Jørgensen et al 2015 - report 2 siblings who are compound heterozygous for COL3A1 sequence variants. One sibling died suddenly due to extensive aortic dissection at age 15. The younger sibling was cerebral cortical dysplasia with thickened frontoparietal cortices bilaterally, small gyri and findings consistent with pachy micropolygyria
Sources: Literature
Malformations of cortical development v4.25 COL3A1 Eleanor Williams gene: COL3A1 was added
gene: COL3A1 was added to Malformations of cortical development. Sources: Literature
Mode of inheritance for gene: COL3A1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COL3A1 were set to 19455184; 25205403; 28742248; 28258187
Phenotypes for gene: COL3A1 were set to Polymicrogyria with or without vascular-type EDS, OMIM:618343; polymicrogyria with or without vascular-type Ehlers-Danlos syndrome, MONDO:0032688
Review for gene: COL3A1 was set to GREEN
Added comment: Associated with Polymicrogyria with or without vascular-type EDS in OMIM (OMIM:618343) with a autosomal recessive mode of inheritance.

Several cases reported:

PMID: 19455184 Plancke et al 2009 - report an 11 year old female with consangiuneous parents, who had vascular EDS. The phenotype also included diffuse cortical dysplasia. A homozygous nucleotide duplication (c.479dupT) in COL3A1 resulting in a premature termination codon (p.Lys161GlnfsX45) was identified. Both parents were heterozygous for this variant.

PMID: 25205403 Jørgensen et al 2015 - report 2 siblings who are compound heterozygous for COL3A1 sequence variants. One sibling died suddenly due to extensive aortic dissection at age 15. The younger sibling was cerebral cortical dysplasia with thickened frontoparietal cortices bilaterally, small gyri and findings consistent with pachy micropolygyria
Sources: Literature
Malformations of cortical development v4.24 PIK3R2 Arina Puzriakova Phenotypes for gene: PIK3R2 were changed from Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1 603387 to Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1, OMIM:603387
Malformations of cortical development v4.23 ASPM Arina Puzriakova Publications for gene: ASPM were set to 12355089
Malformations of cortical development v4.22 ASPM Arina Puzriakova Phenotypes for gene: ASPM were changed from Microcephaly 5, primary, autosomal recessive 608716 to Microcephaly 5, primary, autosomal recessive, OMIM:608716
Malformations of cortical development v4.21 WDR62 Arina Puzriakova Publications for gene: WDR62 were set to
Malformations of cortical development v4.20 WDR62 Arina Puzriakova Phenotypes for gene: WDR62 were changed from Microcephaly 2, primary, autosomal recessive, with or without cortical malformations 604317 to Microcephaly 2, primary, autosomal recessive, with or without cortical malformations, OMIM:604317
Malformations of cortical development v4.19 COL4A1 Achchuthan Shanmugasundram Added comment: Comment on phenotypes: This gene has been associated with relevant phenotypes in both OMIM and Gene2Phenotype (Porencephaly 1 with 'definitive' rating in the DD panel).
Malformations of cortical development v4.19 COL4A1 Achchuthan Shanmugasundram Phenotypes for gene: COL4A1 were changed from Angiopathy, hereditary, with nephropathy, aneurysms, and muscle cramps, OMIM:611773; Brain small vessel disease with or without ocular anomalies, OMIM:175780; Microangiopathy and leukoencephalopathy, pontine, autosomal dominant, OMIM:618564; {Hemorrhage, intracerebral, susceptibility to}, OMIM:614519 to Angiopathy, hereditary, with nephropathy, aneurysms, and muscle cramps, OMIM:611773; Brain small vessel disease with or without ocular anomalies, OMIM:175780; Microangiopathy and leukoencephalopathy, pontine, autosomal dominant, OMIM:618564; {Hemorrhage, intracerebral, susceptibility to}, OMIM:614519
Malformations of cortical development v4.18 COL4A1 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: As reviewed by Nour Elkhateeb, there is sufficient evidence available for the promotion of this gene to green rating in the next GMS review.; to: Comment on list classification: As reviewed by Nour Elkhateeb, there is sufficient evidence available for the promotion of this gene to green rating in the next GMS review.
Malformations of cortical development v4.18 COL4A2 Achchuthan Shanmugasundram Classified gene: COL4A2 as Amber List (moderate evidence)
Malformations of cortical development v4.18 COL4A2 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Nour Elkhateeb, there is sufficient evidence for the promotion of this gene to green rating in the next GMS review.
Malformations of cortical development v4.18 COL4A2 Achchuthan Shanmugasundram Gene: col4a2 has been classified as Amber List (Moderate Evidence).
Malformations of cortical development v4.17 COL4A2 Achchuthan Shanmugasundram changed review comment from: There are at least three unrelated cases of porencephaly reported with monoallelic variants in COL4A2.

This gene has also been associated with relevant phenotypes in both OMIM and Gene2Phenotype (with 'moderate' rating in the DD panel).; to: There are at least three unrelated cases of porencephaly reported with monoallelic variants in COL4A2.

This gene has also been associated with relevant phenotypes in both OMIM and Gene2Phenotype (Porencephaly 2 with 'moderate' rating in the DD panel).
Malformations of cortical development v4.17 COL4A2 Achchuthan Shanmugasundram Phenotypes for gene: COL4A2 were changed from Malformations of cortical development; Schizencephaly; porencephaly; polymicrogyria; focal cortical dysplasia; nodular heterotopia to Brain small vessel disease 2, OMIM:614483; {Hemorrhage, intracerebral, susceptibility to}, OMIM:614519
Malformations of cortical development v4.16 COL4A2 Achchuthan Shanmugasundram Mode of inheritance for gene: COL4A2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Malformations of cortical development v4.15 COL4A2 Achchuthan Shanmugasundram Tag Q4_23_promote_green tag was added to gene: COL4A2.
Tag Q4_23_NHS_review tag was added to gene: COL4A2.
Malformations of cortical development v4.15 COL4A2 Achchuthan Shanmugasundram reviewed gene: COL4A2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Brain small vessel disease 2, OMIM:614483, {Hemorrhage, intracerebral, susceptibility to}, OMIM:614519; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Malformations of cortical development v4.15 COL4A1 Achchuthan Shanmugasundram Tag Q4_23_promote_green tag was added to gene: COL4A1.
Tag Q4_23_NHS_review tag was added to gene: COL4A1.
Malformations of cortical development v4.15 COL4A1 Achchuthan Shanmugasundram Classified gene: COL4A1 as Amber List (moderate evidence)
Malformations of cortical development v4.15 COL4A1 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Nour Elkhateeb, there is sufficient evidence available for the promotion of this gene to green rating in the next GMS review.
Malformations of cortical development v4.15 COL4A1 Achchuthan Shanmugasundram Gene: col4a1 has been classified as Amber List (Moderate Evidence).
Malformations of cortical development v4.14 COL4A1 Achchuthan Shanmugasundram Mode of inheritance for gene: COL4A1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Malformations of cortical development v4.13 COL4A1 Achchuthan Shanmugasundram Phenotypes for gene: COL4A1 were changed from Malformations of cortical development; Schizencephaly; porencephaly; polymicrogyria; focal cortical dysplasia; nodular heterotopia to Angiopathy, hereditary, with nephropathy, aneurysms, and muscle cramps, OMIM:611773; Brain small vessel disease with or without ocular anomalies, OMIM:175780; Microangiopathy and leukoencephalopathy, pontine, autosomal dominant, OMIM:618564; {Hemorrhage, intracerebral, susceptibility to}, OMIM:614519
Malformations of cortical development v4.12 COL4A1 Achchuthan Shanmugasundram reviewed gene: COL4A1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Angiopathy, hereditary, with nephropathy, aneurysms, and muscle cramps, OMIM:611773, Brain small vessel disease with or without ocular anomalies, OMIM:175780, Microangiopathy and leukoencephalopathy, pontine, autosomal dominant, OMIM:618564, {Hemorrhage, intracerebral, susceptibility to}, OMIM:614519; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Malformations of cortical development v4.12 COL4A2 Nour Elkhateeb edited their review of gene: COL4A2: Changed rating: GREEN
Malformations of cortical development v4.12 CASP2 Achchuthan Shanmugasundram Classified gene: CASP2 as Amber List (moderate evidence)
Malformations of cortical development v4.12 CASP2 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Zornitza Stark, there is sufficient evidence available (three unrelated families) for the association of biallelic CASP2 variants with lissencephaly. Hence, this gene can be promoted to green rating in the next GMS update.
Malformations of cortical development v4.12 CASP2 Achchuthan Shanmugasundram Gene: casp2 has been classified as Amber List (Moderate Evidence).
Malformations of cortical development v4.11 CASP2 Achchuthan Shanmugasundram Phenotypes for gene: CASP2 were changed from neurodevelopmental disorder MONDO:0700092, CASP2-related to neurodevelopmental disorder, MONDO:0700092; hereditary cerebral malformation, MONDO:0957008
Malformations of cortical development v4.10 CASP2 Achchuthan Shanmugasundram Tag Q4_23_promote_green tag was added to gene: CASP2.
Malformations of cortical development v4.10 CASP2 Achchuthan Shanmugasundram reviewed gene: CASP2: Rating: GREEN; Mode of pathogenicity: None; Publications: 37880421; Phenotypes: neurodevelopmental disorder, MONDO:0700092, hereditary cerebral malformation, MONDO:0957008; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Malformations of cortical development v4.10 CASP2 Zornitza Stark gene: CASP2 was added
gene: CASP2 was added to Malformations of cortical development. Sources: Literature
Mode of inheritance for gene: CASP2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CASP2 were set to 37880421
Phenotypes for gene: CASP2 were set to neurodevelopmental disorder MONDO:0700092, CASP2-related
Review for gene: CASP2 was set to GREEN
Added comment: 7 individuals from 5 families:
- 4 families homozygous for PTC.
- 1 family compound heterozygote for splice site + PTC. RNA studies indicate usage of 2 cryptic splice donor sites.

5/5 have ID/dev delay
1/5 seizures
2/5 hypotonia
3/5 Lissencephaly (pachygyria + cortical thickening)
Sources: Literature
Malformations of cortical development v4.8 HECTD4 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: HECTD4.
Malformations of cortical development v4.8 HECTD4 Achchuthan Shanmugasundram commented on gene: HECTD4: The OMIM entry for this gene is OMIM:620209, which has been cross-checked with both Ensembl and HGNC. Hence, gene-checked tag has been added.
Malformations of cortical development v4.8 COL4A2 Nour Elkhateeb gene: COL4A2 was added
gene: COL4A2 was added to Malformations of cortical development. Sources: Literature
Mode of inheritance for gene: COL4A2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: COL4A2 were set to 30413629; 36324412; 22333902
Phenotypes for gene: COL4A2 were set to Malformations of cortical development; Schizencephaly; porencephaly; polymicrogyria; focal cortical dysplasia; nodular heterotopia
Added comment: COL4A2 variants are commonly associated with cortical malformations (Schizencephaly, porencephaly, polymicrogyria, focal cortical dysplasia, and nodular heterotopia) in literature.
COL4A2 variants are associated with porencephaly. however, it is not included in the R87 Cerebral malformation panel (indications as per the national genomic test directory include "
Cerebral malformation such as cortical malformation or porencephaly with features suggestive of a monogenic cause"
Sources: Literature
Malformations of cortical development v4.8 COL4A1 Nour Elkhateeb gene: COL4A1 was added
gene: COL4A1 was added to Malformations of cortical development. Sources: Literature
Mode of inheritance for gene: COL4A1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: COL4A1 were set to 30837194; 37157232; 30413629; 36324412
Phenotypes for gene: COL4A1 were set to Malformations of cortical development; Schizencephaly; porencephaly; polymicrogyria; focal cortical dysplasia; nodular heterotopia
Review for gene: COL4A1 was set to GREEN
Added comment: COL4A1 variants are commonly associated with cortical malformations (Schizencephaly, porencephaly, polymicrogyria, focal cortical dysplasia, and nodular heterotopia) in literature. further information available on Genreviews Plaisier E, Ronco P. COL4A1-Related Disorders. 2009 Jun 25 [Updated 2016 Jul 7]. In: Adam MP, Mirzaa GM, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2023. Available from: https://www.ncbi.nlm.nih.gov/books/NBK7046/
COL4A1 variants are associated with porencephaly. however, it is not included in the R87 Cerebral malformation panel (indications as per the national genomic test directory include "
Cerebral malformation such as cortical malformation or porencephaly with features suggestive of a monogenic cause"
Sources: Literature
Malformations of cortical development v4.8 RAC3 Eleanor Williams changed review comment from: The rating of this gene has been updated togreenand the mode of inheritance set to 'MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown' following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to green and the mode of inheritance set to 'MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown' following NHS Genomic Medicine Service approval.
Malformations of cortical development v4.8 RAC3 Eleanor Williams changed review comment from: The rating of this gene has been updated togreenand the mode of inheritance set to'MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown'following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated togreenand the mode of inheritance set to 'MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown' following NHS Genomic Medicine Service approval.
Malformations of cortical development v4.8 SLC35A2 Achchuthan Shanmugasundram Tag Q4_22_promote_green was removed from gene: SLC35A2.
Malformations of cortical development v4.8 RAC3 Achchuthan Shanmugasundram Tag Q2_23_promote_green was removed from gene: RAC3.
Malformations of cortical development v4.8 DEPDC5 Achchuthan Shanmugasundram Tag Q1_23_MOI was removed from gene: DEPDC5.
Malformations of cortical development v4.8 SLC35A2 Eleanor Williams reviewed gene: SLC35A2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Malformations of cortical development v4.8 RAC3 Eleanor Williams reviewed gene: RAC3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Malformations of cortical development v4.8 DEPDC5 Eleanor Williams reviewed gene: DEPDC5: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Malformations of cortical development v4.7 SLC35A2 Achchuthan Shanmugasundram Source Expert Review Green was added to SLC35A2.
Source NHS GMS was added to SLC35A2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Malformations of cortical development v4.7 RAC3 Achchuthan Shanmugasundram Source Expert Review Green was added to RAC3.
Source NHS GMS was added to RAC3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Malformations of cortical development v4.7 DEPDC5 Achchuthan Shanmugasundram Mode of inheritance for gene DEPDC5 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Malformations of cortical development v4.6 HECTD4 Arina Puzriakova Tag Q4_23_promote_green tag was added to gene: HECTD4.
Malformations of cortical development v4.6 HECTD4 Arina Puzriakova Deleted their comment
Malformations of cortical development v4.6 HECTD4 Arina Puzriakova Classified gene: HECTD4 as Amber List (moderate evidence)
Malformations of cortical development v4.6 HECTD4 Arina Puzriakova Gene: hectd4 has been classified as Amber List (Moderate Evidence).
Malformations of cortical development v4.5 HECTD4 Arina Puzriakova Entity copied from Intellectual disability - microarray and sequencing v5.292
Malformations of cortical development v4.5 HECTD4 Arina Puzriakova gene: HECTD4 was added
gene: HECTD4 was added to Malformations of cortical development. Sources: Literature,NHS GMS,Expert Review Green
Mode of inheritance for gene: HECTD4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HECTD4 were set to 36401616
Phenotypes for gene: HECTD4 were set to Neurodevelopmental disorder with seizures, spasticity, and complete or partial agenesis of the corpus callosum, OMIM:620250
Malformations of cortical development v4.4 AKT3 Arina Puzriakova Phenotypes for gene: AKT3 were changed from Polymicrogyria, macrocephaly to Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 2, OMIM:615937
Malformations of cortical development v4.3 RAC3 Arina Puzriakova changed review comment from: Comment on list classification: There are now at least 14 patients from 13 unrelated families with de novo heterozygous variants in this gene (PMIDs: 29276006; 30293988; 35851598; 35595279). Brain imaging has shown variable structural abnormalities in all patients, including cerebral dysgenesis with polymicrogyria and heterotopia in the majority.; to: Comment on list classification: There are now at least 14 patients from 13 unrelated families with de novo heterozygous variants in this gene (PMIDs: 29276006; 30293988; 35851598; 35595279). Brain imaging has shown variable structural abnormalities in all patients, including cerebral dysgenesis with polymicrogyria and heterotopia in the majority. Therefore, this gene can be promoted to Green at the next GMS panel update.
Malformations of cortical development v4.3 RAC3 Arina Puzriakova Classified gene: RAC3 as Amber List (moderate evidence)
Malformations of cortical development v4.3 RAC3 Arina Puzriakova Added comment: Comment on list classification: There are now at least 14 patients from 13 unrelated families with de novo heterozygous variants in this gene (PMIDs: 29276006; 30293988; 35851598; 35595279). Brain imaging has shown variable structural abnormalities in all patients, including cerebral dysgenesis with polymicrogyria and heterotopia in the majority.
Malformations of cortical development v4.3 RAC3 Arina Puzriakova Gene: rac3 has been classified as Amber List (Moderate Evidence).
Malformations of cortical development v4.2 RAC3 Arina Puzriakova Tag Q2_23_promote_green tag was added to gene: RAC3.
Malformations of cortical development v4.2 RAC3 Arina Puzriakova Entity copied from Intellectual disability - microarray and sequencing v5.114
Malformations of cortical development v4.2 RAC3 Arina Puzriakova gene: RAC3 was added
gene: RAC3 was added to Malformations of cortical development. Sources: Literature,Expert Review Green
Mode of inheritance for gene: RAC3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: RAC3 were set to 29276006; 30293988; 35851598; 35595279
Phenotypes for gene: RAC3 were set to Neurodevelopmental disorder with structural brain anomalies and dysmorphic facies, OMIM:618577
Penetrance for gene: RAC3 were set to unknown
Mode of pathogenicity for gene: RAC3 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Malformations of cortical development v4.1 Eleanor Williams Panel version 4.0 has been signed off on 2023-03-22
Malformations of cortical development v4.0 Eleanor Williams promoted panel to version 4.0
Malformations of cortical development v3.12 DEPDC5 Achchuthan Shanmugasundram commented on gene: DEPDC5: The MOI of this gene should be reviewed at the next NHS GMS review on whether it can be updated to 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal'.
Malformations of cortical development v3.12 DEPDC5 Achchuthan Shanmugasundram Tag Q1_23_MOI tag was added to gene: DEPDC5.
Malformations of cortical development v3.12 DEPDC5 Achchuthan Shanmugasundram Publications for gene: DEPDC5 were set to 24585383; 25623524; 31444548; 32848577; 33949696; 34055363
Malformations of cortical development v3.11 DEPDC5 Achchuthan Shanmugasundram changed review comment from: The association of monoallelic variants in DEPDC5 gene to familial focal epilepsy (MIM #604364) have already been established with previous reviews and the existence of this phenotype in both OMIM and Gene2Phenotype.

PMID:32848577 reported a child with a homozygous missense variant (p.Pro1031His) who presented with cortical dysplasia and childhood onset epilepsy.

PMID:36067010 reported homozygous missense variants in five unrelated families (three Irish Traveller families with same variant - p.Thr337Arg; and one Tunisian and one Lebanese families with the same variant - p.Arg806Cys). All nine children from these five families presented with consistent phenotypic features including extensive bilateral polymicrogyria, congenital macrocephaly, early onset refractory epilepsy and severe psychomotor developmental delay. Polymicrogyria is one of the most common malformations of cortical development, characterized by abnormal cortical lamination and excessive folding of the cortical surface

Skin biopsy immunohistochemistry suggested hyperactivation of the mTOR pathway. The disease mechanism is suggested as 'loss of function' as DEPDC5 is a repressor/inhibitor within the mTOR pathway.

The phenotypes caused by biallelic variants are not yet reported in OMIM or in Gene2Phenotype.; to: The association of monoallelic variants in DEPDC5 gene to familial focal epilepsy (MIM #604364) have already been established with previous reviews and the existence of this phenotype in both OMIM and Gene2Phenotype.

PMID:32848577 reported a child with a homozygous missense variant (p.Pro1031His) who presented with cortical dysplasia and childhood onset epilepsy.

PMID:36067010 reported homozygous missense variants in five unrelated families (three Irish Traveller families with same variant - p.Thr337Arg; and one Tunisian and one Lebanese families with the same variant - p.Arg806Cys). All nine children from these five families presented with consistent phenotypic features including extensive bilateral polymicrogyria, congenital macrocephaly, early onset refractory epilepsy and severe psychomotor developmental delay. Polymicrogyria is one of the most common malformations of cortical development, characterized by abnormal cortical lamination and excessive folding of the cortical surface. Skin biopsy immunohistochemistry suggested hyperactivation of the mTOR pathway. The disease mechanism is suggested as 'loss of function' as DEPDC5 is a repressor/inhibitor within the mTOR pathway.

The phenotypes caused by biallelic variants are not yet reported in OMIM or in Gene2Phenotype.
Malformations of cortical development v3.11 DEPDC5 Achchuthan Shanmugasundram reviewed gene: DEPDC5: Rating: GREEN; Mode of pathogenicity: None; Publications: 32848577, 36067010; Phenotypes: Epilepsy, familial focal, with variable foci 1, OMIM:604364, epilepsy, MONDO:0005027, Macrocephaly, HP:0000256, polymicrogyria, MONDO:0000087, cerebral cortical dysplasia, MONDO:0017094, neurodevelopmental disorder, MONDO:0700092; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Malformations of cortical development v3.11 WNK3 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: WNK3.
Malformations of cortical development v3.11 DAG1 Arina Puzriakova Tag Q3_22_rating was removed from gene: DAG1.
Tag Q3_22_expert_review was removed from gene: DAG1.
Malformations of cortical development v3.11 DAG1 Arina Puzriakova changed review comment from: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains Green.; to: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains Green. Additional commends from reviewing GLHs: "Clearly disease-causing. Cobblestone lissencephaly is a feature of MDDGC disorders and probably overlaps this panel. Reasonable to retain I think."
Malformations of cortical development v3.11 TP73 Arina Puzriakova Tag Q3_21_rating was removed from gene: TP73.
Malformations of cortical development v3.11 TBC1D32 Arina Puzriakova Tag Q3_21_rating was removed from gene: TBC1D32.
Malformations of cortical development v3.11 SOX11 Arina Puzriakova Tag Q2_22_rating was removed from gene: SOX11.
Tag Q2_22_NHS_review was removed from gene: SOX11.
Malformations of cortical development v3.11 SCN3A Arina Puzriakova Tag Q4_21_rating was removed from gene: SCN3A.
Malformations of cortical development v3.11 RAB3GAP2 Arina Puzriakova Tag Q4_21_rating was removed from gene: RAB3GAP2.
Malformations of cortical development v3.11 RAB3GAP1 Arina Puzriakova Tag Q4_21_rating was removed from gene: RAB3GAP1.
Malformations of cortical development v3.11 RAB18 Arina Puzriakova Tag Q4_21_rating was removed from gene: RAB18.
Malformations of cortical development v3.11 PTEN Arina Puzriakova Tag Q4_21_rating was removed from gene: PTEN.
Malformations of cortical development v3.11 PIDD1 Arina Puzriakova Tag Q3_21_rating was removed from gene: PIDD1.
Malformations of cortical development v3.11 PI4KA Arina Puzriakova Tag Q4_21_rating was removed from gene: PI4KA.
Malformations of cortical development v3.11 PEX6 Arina Puzriakova Tag Q1_22_MOI was removed from gene: PEX6.
Malformations of cortical development v3.11 NPRL3 Arina Puzriakova Tag Q4_21_rating was removed from gene: NPRL3.
Malformations of cortical development v3.11 NPRL2 Arina Puzriakova Tag Q4_21_rating was removed from gene: NPRL2.
Malformations of cortical development v3.11 MAPK8IP3 Arina Puzriakova Tag Q4_21_rating was removed from gene: MAPK8IP3.
Malformations of cortical development v3.11 GRIN2B Arina Puzriakova Tag Q4_21_rating was removed from gene: GRIN2B.
Malformations of cortical development v3.11 GRIN1 Arina Puzriakova Tag Q3_21_rating was removed from gene: GRIN1.
Malformations of cortical development v3.11 EML1 Arina Puzriakova Tag Q3_21_rating was removed from gene: EML1.
Malformations of cortical development v3.11 DPYSL5 Arina Puzriakova Tag Q3_21_rating was removed from gene: DPYSL5.
Malformations of cortical development v3.11 DEPDC5 Arina Puzriakova Tag Q3_21_rating was removed from gene: DEPDC5.
Malformations of cortical development v3.11 DCHS1 Arina Puzriakova Tag Q3_21_rating was removed from gene: DCHS1.
Malformations of cortical development v3.11 CTNNA2 Arina Puzriakova Tag Q3_21_rating was removed from gene: CTNNA2.
Malformations of cortical development v3.11 B4GAT1 Arina Puzriakova Tag Q3_21_rating was removed from gene: B4GAT1.
Malformations of cortical development v3.11 ATP1A3 Arina Puzriakova Tag Q4_21_rating was removed from gene: ATP1A3.
Malformations of cortical development v3.11 ARF1 Arina Puzriakova Tag Q3_21_rating was removed from gene: ARF1.
Malformations of cortical development v3.11 PEX7 Arina Puzriakova Tag Q3_21_rating was removed from gene: PEX7.
Tag Q3_21_expert_review was removed from gene: PEX7.
Malformations of cortical development v3.11 EMX2 Arina Puzriakova Tag Q2_22_rating was removed from gene: EMX2.
Tag Q2_22_expert_review was removed from gene: EMX2.
Malformations of cortical development v3.11 NSRP1 Arina Puzriakova Tag Q3_22_rating was removed from gene: NSRP1.
Malformations of cortical development v3.11 DAG1 Arina Puzriakova commented on gene: DAG1
Malformations of cortical development v3.11 TP73 Arina Puzriakova commented on gene: TP73: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.
Malformations of cortical development v3.11 TBC1D32 Arina Puzriakova reviewed gene: TBC1D32: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Malformations of cortical development v3.11 SOX11 Arina Puzriakova reviewed gene: SOX11: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Malformations of cortical development v3.11 SCN3A Arina Puzriakova reviewed gene: SCN3A: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Malformations of cortical development v3.11 RAB3GAP2 Arina Puzriakova reviewed gene: RAB3GAP2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Malformations of cortical development v3.11 RAB3GAP1 Arina Puzriakova reviewed gene: RAB3GAP1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Malformations of cortical development v3.11 RAB18 Arina Puzriakova reviewed gene: RAB18: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Malformations of cortical development v3.11 PTEN Arina Puzriakova reviewed gene: PTEN: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Malformations of cortical development v3.11 PIDD1 Arina Puzriakova commented on gene: PIDD1: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.
Malformations of cortical development v3.11 PI4KA Arina Puzriakova reviewed gene: PI4KA: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Malformations of cortical development v3.11 PEX6 Arina Puzriakova commented on gene: PEX6
Malformations of cortical development v3.11 NPRL3 Arina Puzriakova reviewed gene: NPRL3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Malformations of cortical development v3.11 NPRL2 Arina Puzriakova reviewed gene: NPRL2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Malformations of cortical development v3.11 MAPK8IP3 Arina Puzriakova edited their review of gene: MAPK8IP3: Added comment: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.; Changed rating: GREEN
Malformations of cortical development v3.11 GRIN2B Arina Puzriakova reviewed gene: GRIN2B: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Malformations of cortical development v3.11 GRIN1 Arina Puzriakova reviewed gene: GRIN1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Malformations of cortical development v3.11 EML1 Arina Puzriakova edited their review of gene: EML1: Added comment: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.; Changed rating: GREEN
Malformations of cortical development v3.11 DPYSL5 Arina Puzriakova reviewed gene: DPYSL5: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Malformations of cortical development v3.11 DEPDC5 Arina Puzriakova edited their review of gene: DEPDC5: Added comment: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.; Changed rating: GREEN
Malformations of cortical development v3.11 DCHS1 Arina Puzriakova edited their review of gene: DCHS1: Added comment: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.; Changed rating: GREEN
Malformations of cortical development v3.11 CTNNA2 Arina Puzriakova edited their review of gene: CTNNA2: Added comment: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.; Changed rating: GREEN
Malformations of cortical development v3.11 B4GAT1 Arina Puzriakova reviewed gene: B4GAT1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Malformations of cortical development v3.11 ATP1A3 Arina Puzriakova reviewed gene: ATP1A3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Malformations of cortical development v3.11 ARF1 Arina Puzriakova edited their review of gene: ARF1: Added comment: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.; Changed rating: GREEN
Malformations of cortical development v3.11 PEX7 Arina Puzriakova edited their review of gene: PEX7: Added comment: The rating of this gene has been updated to Red following NHS Genomic Medicine Service approval.; Changed rating: RED
Malformations of cortical development v3.11 EMX2 Arina Puzriakova reviewed gene: EMX2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Malformations of cortical development v3.11 NSRP1 Arina Puzriakova edited their review of gene: NSRP1: Added comment: The rating of this gene has been updated to Green and the mode of inheritance set to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.; Changed rating: GREEN
Malformations of cortical development v3.10 TP73 Arina Puzriakova Source Expert Review Green was added to TP73.
Source NHS GMS was added to TP73.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Malformations of cortical development v3.10 TBC1D32 Arina Puzriakova Source Expert Review Green was added to TBC1D32.
Source NHS GMS was added to TBC1D32.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Malformations of cortical development v3.10 SOX11 Arina Puzriakova Source Expert Review Green was added to SOX11.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Malformations of cortical development v3.10 SCN3A Arina Puzriakova Source Expert Review Green was added to SCN3A.
Source NHS GMS was added to SCN3A.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Malformations of cortical development v3.10 RAB3GAP2 Arina Puzriakova Source Expert Review Green was added to RAB3GAP2.
Source NHS GMS was added to RAB3GAP2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Malformations of cortical development v3.10 RAB3GAP1 Arina Puzriakova Source Expert Review Green was added to RAB3GAP1.
Source NHS GMS was added to RAB3GAP1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Malformations of cortical development v3.10 RAB18 Arina Puzriakova Source Expert Review Green was added to RAB18.
Source NHS GMS was added to RAB18.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Malformations of cortical development v3.10 PTEN Arina Puzriakova Source Expert Review Green was added to PTEN.
Source NHS GMS was added to PTEN.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Malformations of cortical development v3.10 PIDD1 Arina Puzriakova Source Expert Review Green was added to PIDD1.
Source NHS GMS was added to PIDD1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Malformations of cortical development v3.10 PI4KA Arina Puzriakova Source Expert Review Green was added to PI4KA.
Source NHS GMS was added to PI4KA.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Malformations of cortical development v3.10 PEX7 Arina Puzriakova Source NHS GMS was added to PEX7.
Source Expert Review Red was added to PEX7.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Malformations of cortical development v3.10 PEX6 Arina Puzriakova Source NHS GMS was added to PEX6.
Mode of inheritance for gene PEX6 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Malformations of cortical development v3.10 NSRP1 Arina Puzriakova Source Expert Review Green was added to NSRP1.
Source NHS GMS was added to NSRP1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Malformations of cortical development v3.10 NPRL3 Arina Puzriakova Source Expert Review Green was added to NPRL3.
Source NHS GMS was added to NPRL3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Malformations of cortical development v3.10 NPRL2 Arina Puzriakova Source Expert Review Green was added to NPRL2.
Source NHS GMS was added to NPRL2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Malformations of cortical development v3.10 MAPK8IP3 Arina Puzriakova Source Expert Review Green was added to MAPK8IP3.
Source NHS GMS was added to MAPK8IP3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Malformations of cortical development v3.10 GRIN2B Arina Puzriakova Source Expert Review Green was added to GRIN2B.
Source NHS GMS was added to GRIN2B.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Malformations of cortical development v3.10 GRIN1 Arina Puzriakova Source Expert Review Green was added to GRIN1.
Source NHS GMS was added to GRIN1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Malformations of cortical development v3.10 EMX2 Arina Puzriakova Source NHS GMS was added to EMX2.
Source Expert Review Amber was added to EMX2.
Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
Malformations of cortical development v3.10 EML1 Arina Puzriakova Source Expert Review Green was added to EML1.
Source NHS GMS was added to EML1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Malformations of cortical development v3.10 DPYSL5 Arina Puzriakova Source Expert Review Green was added to DPYSL5.
Source NHS GMS was added to DPYSL5.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Malformations of cortical development v3.10 DEPDC5 Arina Puzriakova Source Expert Review Green was added to DEPDC5.
Source NHS GMS was added to DEPDC5.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Malformations of cortical development v3.10 DCHS1 Arina Puzriakova Source Expert Review Green was added to DCHS1.
Source NHS GMS was added to DCHS1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Malformations of cortical development v3.10 CTNNA2 Arina Puzriakova Source Expert Review Green was added to CTNNA2.
Source NHS GMS was added to CTNNA2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Malformations of cortical development v3.10 B4GAT1 Arina Puzriakova Source Expert Review Green was added to B4GAT1.
Source NHS GMS was added to B4GAT1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Malformations of cortical development v3.10 ATP1A3 Arina Puzriakova Source Expert Review Green was added to ATP1A3.
Source NHS GMS was added to ATP1A3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Malformations of cortical development v3.10 ARF1 Arina Puzriakova Source Expert Review Green was added to ARF1.
Source NHS GMS was added to ARF1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Malformations of cortical development v3.9 TUBB2B Arina Puzriakova Phenotypes for gene: TUBB2B were changed from Polymicrogyria, symmetric or asymmetric 610031 to Cortical dysplasia, complex, with other brain malformations 7, OMIM:610031
Malformations of cortical development v3.8 SLC35A2 Arina Puzriakova Tag Q4_22_expert_review was removed from gene: SLC35A2.
Tag mosaicism tag was added to gene: SLC35A2.
Tag somatic tag was added to gene: SLC35A2.
Malformations of cortical development v3.8 SLC35A2 Arina Puzriakova Phenotypes for gene: SLC35A2 were changed from Mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy (MOGHE) to Mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy (MOGHE); Congenital disorder of glycosylation, type IIm, OMIM:300896
Malformations of cortical development v3.7 SLC35A2 Arina Puzriakova Publications for gene: SLC35A2 were set to 33407896
Malformations of cortical development v3.6 SLC35A2 Arina Puzriakova Classified gene: SLC35A2 as Amber List (moderate evidence)
Malformations of cortical development v3.6 SLC35A2 Arina Puzriakova Added comment: Comment on list classification: There is sufficient evidence to support this gene-disease association and regardless of ability to detect somatic variants via this panel, there are enough cases with germline variants to warrant inclusion with a Green classification. Somatic cases should be picked up via other routes such as R429 'Mosaic brain disorders - deep sequencing' which is catered to somatic variant detection.
Malformations of cortical development v3.6 SLC35A2 Arina Puzriakova Gene: slc35a2 has been classified as Amber List (Moderate Evidence).
Malformations of cortical development v3.5 SLC35A2 Arina Puzriakova Tag Q4_22_promote_green tag was added to gene: SLC35A2.
Tag Q4_22_expert_review tag was added to gene: SLC35A2.
Malformations of cortical development v3.5 PAFAH1B1 Arina Puzriakova Phenotypes for gene: PAFAH1B1 were changed from Lissencephaly 1 607432; Subcortical laminar heterotopia 607432 to Lissencephaly 1, OMIM:607432; Subcortical laminar heterotopia, OMIM:607432
Malformations of cortical development v3.4 DCX Arina Puzriakova Phenotypes for gene: DCX were changed from Lissencephaly, X-linked 300067; Subcortical laminal heteropia, X-linked 300067; Classic Lissencephaly/Subcortical Band Heterotopia to Lissencephaly, X-linked, OMIM:300067; Subcortical laminal heterotopia, X-linked, OMIM:300067
Malformations of cortical development v3.3 CASK Arina Puzriakova Publications for gene: CASK were set to 21954287; 20595373; 32700313; 33090494; 33272775
Malformations of cortical development v3.2 PAFAH1B1 Achchuthan Shanmugasundram Publications for gene: PAFAH1B1 were set to
Malformations of cortical development v3.1 PAFAH1B1 Achchuthan Shanmugasundram reviewed gene: PAFAH1B1: Rating: ; Mode of pathogenicity: None; Publications: 34635911; Phenotypes: ; Mode of inheritance: None
Malformations of cortical development v3.1 Achchuthan Shanmugasundram Panel version 3.0 has been signed off on 2022-11-30
Malformations of cortical development v3.0 Achchuthan Shanmugasundram promoted panel to version 3.0
Malformations of cortical development v2.149 DAG1 Eleanor Williams commented on gene: DAG1
Malformations of cortical development v2.149 DAG1 Eleanor Williams Tag Q4_21_expert_review was removed from gene: DAG1.
Tag Q3_22_rating tag was added to gene: DAG1.
Tag Q3_22_expert_review tag was added to gene: DAG1.
Malformations of cortical development v2.149 TBC1D32 Sarah Leigh Publications for gene: TBC1D32 were set to 32573025; 31130284; 32060556; 24285566
Malformations of cortical development v2.148 NSRP1 Arina Puzriakova Entity copied from Intellectual disability v3.1641
Malformations of cortical development v2.148 NSRP1 Arina Puzriakova gene: NSRP1 was added
gene: NSRP1 was added to Malformations of cortical development. Sources: Expert Review Amber,Literature
Q3_22_rating tags were added to gene: NSRP1.
Mode of inheritance for gene: NSRP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NSRP1 were set to 34385670
Phenotypes for gene: NSRP1 were set to NSRP1-associated developmental delay, epilepsy and microcephaly
Malformations of cortical development v2.147 TUBG1 Arina Puzriakova Publications for gene: TUBG1 were set to 23603762; 27010057
Malformations of cortical development v2.146 WNK3 Arina Puzriakova Classified gene: WNK3 as Amber List (moderate evidence)
Malformations of cortical development v2.146 WNK3 Arina Puzriakova Added comment: Comment on list classification: Brain phenotypes in cases reported to date are varied and non-specific. Therefore, rating Amber with a watchlist tag to allow monitoring for future cases which may indicate whether brain malformations are a prominent features of this disorder.
Malformations of cortical development v2.146 WNK3 Arina Puzriakova Gene: wnk3 has been classified as Amber List (Moderate Evidence).
Malformations of cortical development v2.145 WNK3 Arina Puzriakova gene: WNK3 was added
gene: WNK3 was added to Malformations of cortical development. Sources: Literature
watchlist tags were added to gene: WNK3.
Mode of inheritance for gene: WNK3 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: WNK3 were set to 35678782
Phenotypes for gene: WNK3 were set to Intellectual disability, MONDO:0001071
Added comment: Kury et al. 2022 (PMID: 35678782) reported 14 males from 6 unrelated families with hemizygous variants (3 LOF and 3 missense, predicted pathogenic) in the WNK3 gene. All (14/14) had DD/ID and variable other associations including seizures (5/13), mild microcephaly (6/13, ranging -2 to -2.4 SD) and structural brain malformations (7/10). Heterozygous mothers were all asymptomatic.

Brain imaging in 4 families that had anomalies showed F1) polymicrogyria in two sibs, F2) mild cerebral atrophy and bilateral periventricular white matter hypersignal, F3) three patients with subcortical cerebral atrophy, dilation of lateral ventricles, and F4) symmetric T2 prolongation involving the deep gray structures, central tegmental tracts and dentate nuclei.
Sources: Literature
Malformations of cortical development v2.144 EMX2 Sarah Leigh Publications for gene: EMX2 were set to 8528262; 9359037; 18409201
Malformations of cortical development v2.143 EMX2 Sarah Leigh reviewed gene: EMX2: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: 18409201, 17506092; Mode of inheritance: None
Malformations of cortical development v2.143 EMX2 Sarah Leigh Tag Q2_22_rating tag was added to gene: EMX2.
Tag Q2_22_expert_review tag was added to gene: EMX2.
Malformations of cortical development v2.143 SOX11 Sarah Leigh edited their review of gene: SOX11: Added comment: Associated with relevant phenotype in OMIM and as strong Gen2Phen gene. SOX11 variants have been reported by the NHS, including one from Tracy Lester and de novo variants in around 20 children with overlapping clinical features by Alisdair mcneill (Sheffield childrens hospital)(7 Oct 2019).; Changed rating: GREEN
Malformations of cortical development v2.143 SOX11 Sarah Leigh Added comment: Comment on phenotypes: Described as MENTAL RETARDATION, AUTOSOMAL DOMINANT, 27 by Gen2Phen (https://www.ebi.ac.uk/gene2phenotype/gfd?dbID=405).
Malformations of cortical development v2.143 SOX11 Sarah Leigh Phenotypes for gene: SOX11 were changed from intellectual disability; facial dysmorphism; microcephaly; digit anomalies; central nervous system malformations to Coffin-Siris syndrome 9, OMIM:615866
Malformations of cortical development v2.142 SOX11 Sarah Leigh Classified gene: SOX11 as Amber List (moderate evidence)
Malformations of cortical development v2.142 SOX11 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Malformations of cortical development v2.142 SOX11 Sarah Leigh Gene: sox11 has been classified as Amber List (Moderate Evidence).
Malformations of cortical development v2.141 SOX11 Sarah Leigh Tag Q2_22_rating tag was added to gene: SOX11.
Tag Q2_22_NHS_review tag was added to gene: SOX11.
Malformations of cortical development v2.141 TUBGCP2 Arina Puzriakova Tag gene-checked tag was added to gene: TUBGCP2.
Malformations of cortical development v2.141 TBC1D32 Eleanor Williams Tag gene-checked tag was added to gene: TBC1D32.
Malformations of cortical development v2.141 CEP85L Eleanor Williams Tag gene-checked tag was added to gene: CEP85L.
Malformations of cortical development v2.141 SOX11 Tracy Lester gene: SOX11 was added
gene: SOX11 was added to Malformations of cortical development. Sources: NHS GMS
Mode of inheritance for gene: SOX11 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SOX11 were set to 24886874; 26543203; 23556151
Phenotypes for gene: SOX11 were set to intellectual disability; facial dysmorphism; microcephaly; digit anomalies; central nervous system malformations
Penetrance for gene: SOX11 were set to unknown
Review for gene: SOX11 was set to GREEN
Added comment: Coffin-Siris syndrome is associated with brain malformations and variable ID. A pathogenic variant in this gene was identified in a case with brain malformations who had R87 panel applied but not R29 or R27. The gene is already green on these other panels.
Sources: NHS GMS
Malformations of cortical development v2.141 PEX6 Sarah Leigh Penetrance for gene PEX6 was set from to None
Malformations of cortical development v2.140 PEX6 Sarah Leigh edited their review of gene: PEX6: Added comment: For Peroxisome biogenesis disorder 4B (OMIM:614863), Falkenberg et al (PMID: 29220678) has identified Allelic Expression Imbalance (AEI) as a mechanism responsible for the condition. Affected patients (7 unrelated cases) were monoallelic for rs61753230 (c.2578C>T, p.Arg860Trp) and rs144286892 (c.∗442_445 delTAAA), with these variants being on the same chromosome (cis). It would appear that rs144286892 causes the over expression of the allele that it is on, resulting in over expression of rs61753230. The unaffected parents analysed were monoallelic for rs61753230 and biallelic for rs144286892, resulting in overexpression of both rs61753230 and wild type alleles (PMID: 29220678). Experimental evidence revealed that rs61753230 has a dominant-negative effect on the function of the PEX1- PEX6 complex in peroxisomal matrix protein import (PMID: 29220678).; Changed mode of pathogenicity: Other; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Malformations of cortical development v2.140 PEX6 Sarah Leigh Tag Q1_22_MOI tag was added to gene: PEX6.
Malformations of cortical development v2.140 PEX6 Sarah Leigh Added comment: Comment on mode of inheritance: The Q1_22_MOI tag has been added to this gene. The mode of inheritance for PEX6 should be set to: BOTH monoallelic and biallelic, autosomal or pseudoautosomal, in order to detect the dominant Peroxisome biogenesis disorder 4B (OMIM:614863). Incomplete penetrance has been noted, in order to highlight that unaffected parents may also carry rs61753230.
Malformations of cortical development v2.140 PEX6 Sarah Leigh Mode of inheritance for gene: PEX6 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Malformations of cortical development v2.139 PEX6 Sarah Leigh Phenotypes for gene: PEX6 were changed from Disorders of peroxisome biogenesis; Peroxisome biogenesis disorder 4A (Zellweger), 614862; Peroxisome biogenesis disorder 4B, 614863 to Peroxisome biogenesis disorder 4A (Zellweger), OMIM:614862; Peroxisome biogenesis disorder 4B, OMIM:614863
Malformations of cortical development v2.138 PEX6 Sarah Leigh Publications for gene: PEX6 were set to 27604308
Malformations of cortical development v2.137 ISCA-37430-Loss Arina Puzriakova commented on Region: ISCA-37430-Loss
Malformations of cortical development v2.137 ISCA-37430-Loss Arina Puzriakova Required Overlap Percentage for ISCA-37430-Loss was changed from 80 to 60.
Malformations of cortical development v2.136 CRADD Eleanor Williams Tag Q3_21_rating was removed from gene: CRADD.
Malformations of cortical development v2.136 CRADD Sarah Leigh commented on gene: CRADD
Malformations of cortical development v2.135 CRADD Eleanor Williams Source Expert Review Green was added to CRADD.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Malformations of cortical development v2.134 MAP1B Eleanor Williams Phenotypes for gene: MAP1B were changed from Periventricular nodular heterotopia 9, MIM# 618918 to Periventricular nodular heterotopia 9, OMIM:618918
Malformations of cortical development v2.133 MAP1B Eleanor Williams Tag for-review was removed from gene: MAP1B.
Malformations of cortical development v2.133 H3F3A Eleanor Williams Tag for-review was removed from gene: H3F3A.
Malformations of cortical development v2.133 CDH2 Eleanor Williams Tag for-review was removed from gene: CDH2.
Malformations of cortical development v2.133 LAMA2 Eleanor Williams Tag for-review was removed from gene: LAMA2.
Malformations of cortical development v2.133 CASK Eleanor Williams Tag for-review was removed from gene: CASK.
Malformations of cortical development v2.133 VLDLR Eleanor Williams Tag for-review was removed from gene: VLDLR.
Malformations of cortical development v2.133 ATP1A2 Eleanor Williams Tag for-review was removed from gene: ATP1A2.
Malformations of cortical development v2.133 CEP85L Eleanor Williams Tag for-review was removed from gene: CEP85L.
Malformations of cortical development v2.133 TMX2 Eleanor Williams Tag for-review was removed from gene: TMX2.
Malformations of cortical development v2.133 TUBGCP2 Eleanor Williams Phenotypes for gene: TUBGCP2 were changed from Pachygyria, microcephaly, developmental delay, and dysmorphic facies, with or without seizures, 618737 to Pachygyria, microcephaly, developmental delay, and dysmorphic facies, with or without seizures, OMIM:618737
Malformations of cortical development v2.132 TUBGCP2 Eleanor Williams Tag for-review was removed from gene: TUBGCP2.
Malformations of cortical development v2.132 PPP1R12A Eleanor Williams Phenotypes for gene: PPP1R12A were changed from Genitourinary and/or/brain malformation syndrome, 618820 to Genitourinary and/or/brain malformation syndrome, OMIM:618820
Malformations of cortical development v2.131 PPP1R12A Eleanor Williams Tag for-review was removed from gene: PPP1R12A.
Malformations of cortical development v2.131 MN1 Eleanor Williams Tag for-review was removed from gene: MN1.
Malformations of cortical development v2.131 SNAP29 Eleanor Williams Tag for-review was removed from gene: SNAP29.
Malformations of cortical development v2.131 APC2 Eleanor Williams Tag for-review was removed from gene: APC2.
Malformations of cortical development v2.131 MAP1B Sarah Leigh commented on gene: MAP1B
Malformations of cortical development v2.131 H3F3A Sarah Leigh commented on gene: H3F3A
Malformations of cortical development v2.131 CDH2 Sarah Leigh commented on gene: CDH2
Malformations of cortical development v2.131 LAMA2 Sarah Leigh commented on gene: LAMA2: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Malformations of cortical development v2.131 CASK Sarah Leigh commented on gene: CASK: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Malformations of cortical development v2.131 VLDLR Sarah Leigh commented on gene: VLDLR: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Malformations of cortical development v2.131 ATP1A2 Sarah Leigh commented on gene: ATP1A2
Malformations of cortical development v2.131 CEP85L Sarah Leigh commented on gene: CEP85L
Malformations of cortical development v2.131 TMX2 Sarah Leigh commented on gene: TMX2: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Malformations of cortical development v2.131 TUBGCP2 Sarah Leigh commented on gene: TUBGCP2
Malformations of cortical development v2.131 PPP1R12A Sarah Leigh commented on gene: PPP1R12A
Malformations of cortical development v2.131 MN1 Sarah Leigh commented on gene: MN1
Malformations of cortical development v2.131 SNAP29 Sarah Leigh commented on gene: SNAP29
Malformations of cortical development v2.131 APC2 Sarah Leigh commented on gene: APC2: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Malformations of cortical development v2.130 MAP1B Eleanor Williams Source Expert Review Green was added to MAP1B.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Malformations of cortical development v2.130 H3F3A Eleanor Williams Source Expert Review Green was added to H3F3A.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Malformations of cortical development v2.130 CDH2 Eleanor Williams Source Expert Review Green was added to CDH2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Malformations of cortical development v2.130 LAMA2 Eleanor Williams Source Expert Review Green was added to LAMA2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Malformations of cortical development v2.130 CASK Eleanor Williams Source Expert Review Green was added to CASK.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Malformations of cortical development v2.130 VLDLR Eleanor Williams Source Expert Review Green was added to VLDLR.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Malformations of cortical development v2.130 ATP1A2 Eleanor Williams Source Expert Review Green was added to ATP1A2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Malformations of cortical development v2.130 CEP85L Eleanor Williams Source Expert Review Green was added to CEP85L.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Malformations of cortical development v2.130 TMX2 Eleanor Williams Source Expert Review Green was added to TMX2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Malformations of cortical development v2.130 TUBGCP2 Eleanor Williams Source Expert Review Green was added to TUBGCP2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Malformations of cortical development v2.130 PPP1R12A Eleanor Williams Source Expert Review Green was added to PPP1R12A.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Malformations of cortical development v2.130 MN1 Eleanor Williams Source Expert Review Green was added to MN1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Malformations of cortical development v2.130 SNAP29 Eleanor Williams Source Expert Review Green was added to SNAP29.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Malformations of cortical development v2.130 APC2 Eleanor Williams Source Expert Review Green was added to APC2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Malformations of cortical development v2.129 RAB3GAP2 Sarah Leigh Phenotypes for gene: RAB3GAP2 were changed from Warburg micro syndrome 2, OMIM:614225 to Warburg micro syndrome 2, OMIM:614225; Warburg micro syndrome 2 MONDO:0013641
Malformations of cortical development v2.128 RAB3GAP2 Sarah Leigh Publications for gene: RAB3GAP2 were set to 23420520; 20967465
Malformations of cortical development v2.127 RAB3GAP2 Sarah Leigh Tag Q4_21_rating tag was added to gene: RAB3GAP2.
Malformations of cortical development v2.127 RAB3GAP2 Sarah Leigh edited their review of gene: RAB3GAP2: Added comment: Associated with relevant phenotype in OMIM, but not associated with Warburg micro syndrome 2 OMIM:614225 in Gen2Phen. At least four variants reported in at least four unrelated cases..; Changed rating: GREEN
Malformations of cortical development v2.127 RAB3GAP2 Sarah Leigh Classified gene: RAB3GAP2 as Amber List (moderate evidence)
Malformations of cortical development v2.127 RAB3GAP2 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Malformations of cortical development v2.127 RAB3GAP2 Sarah Leigh Gene: rab3gap2 has been classified as Amber List (Moderate Evidence).
Malformations of cortical development v2.126 RAB3GAP1 Sarah Leigh Publications for gene: RAB3GAP1 were set to 23420520; 32740904
Malformations of cortical development v2.125 RAB3GAP1 Sarah Leigh edited their review of gene: RAB3GAP1: Added comment: Associated with relevant phenotype in OMIM and as definitive Gen2Phen gene. At least 13 variants reported in at least 12 unrelated cases; Changed rating: GREEN
Malformations of cortical development v2.125 RAB3GAP1 Sarah Leigh Phenotypes for gene: RAB3GAP1 were changed from Warburg micro syndrome 1, OMIM:600118 to Warburg micro syndrome 1 OMIM:600118; Warburg micro syndrome 1 MONDO:0010822
Malformations of cortical development v2.124 RAB3GAP1 Sarah Leigh Tag Q4_21_rating tag was added to gene: RAB3GAP1.
Malformations of cortical development v2.124 RAB3GAP1 Sarah Leigh Classified gene: RAB3GAP1 as Amber List (moderate evidence)
Malformations of cortical development v2.124 RAB3GAP1 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Malformations of cortical development v2.124 RAB3GAP1 Sarah Leigh Gene: rab3gap1 has been classified as Amber List (Moderate Evidence).
Malformations of cortical development v2.123 DAG1 Sarah Leigh Classified gene: DAG1 as Green List (high evidence)
Malformations of cortical development v2.123 DAG1 Sarah Leigh Added comment: Comment on list classification: There is not enough evidence for this gene to be rated GREEN at the next major review.
Malformations of cortical development v2.123 DAG1 Sarah Leigh Gene: dag1 has been classified as Green List (High Evidence).
Malformations of cortical development v2.122 DAG1 Sarah Leigh reviewed gene: DAG1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Malformations of cortical development v2.122 DAG1 Sarah Leigh Tag Q4_21_expert_review tag was added to gene: DAG1.
Malformations of cortical development v2.122 DAG1 Sarah Leigh Publications for gene: DAG1 were set to 24052401; 25934851
Malformations of cortical development v2.121 DAG1 Sarah Leigh Publications for gene: DAG1 were set to 24052401
Malformations of cortical development v2.120 PTEN Sarah Leigh edited their review of gene: PTEN: Added comment: In the retrospective study PMID: 32162846, the authors observe four unrelated cases who exhibit polymicrogyria.; Changed rating: GREEN
Malformations of cortical development v2.120 PTEN Sarah Leigh Tag Q4_21_rating tag was added to gene: PTEN.
Malformations of cortical development v2.120 PTEN Sarah Leigh Classified gene: PTEN as Amber List (moderate evidence)
Malformations of cortical development v2.120 PTEN Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Malformations of cortical development v2.120 PTEN Sarah Leigh Gene: pten has been classified as Amber List (Moderate Evidence).
Malformations of cortical development v2.119 PTEN Sarah Leigh Phenotypes for gene: PTEN were changed from Cowden syndrome 1 158350; Lhermitte-Duclos syndrome 158350; Macrocephaly/autism syndrome 605309 to Cowden syndrome 1 OMIM:158350; Lhermitte-Duclos syndrome OMIM:158350; Cowden syndrome 1 MONDO:0008021; Macrocephaly/autism syndrome OMIM:605309; macrocephaly-autism syndrome MONDO:0011537
Malformations of cortical development v2.118 RAB3GAP1 Ivone Leong Added comment: Comment on publications: More cases PMID: 32740904
Malformations of cortical development v2.118 RAB3GAP1 Ivone Leong Publications for gene: RAB3GAP1 were set to 23420520
Malformations of cortical development v2.117 RAB3GAP1 Ivone Leong Phenotypes for gene: RAB3GAP1 were changed from Warburg micro syndrome 1, MIM# 600118 to Warburg micro syndrome 1, OMIM:600118
Malformations of cortical development v2.116 RAB18 Ivone Leong Tag Q4_21_rating tag was added to gene: RAB18.
Malformations of cortical development v2.116 RAB18 Ivone Leong Classified gene: RAB18 as Amber List (moderate evidence)
Malformations of cortical development v2.116 RAB18 Ivone Leong Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is associated with a relevant phenotype in OMIM and Gene2Phenotype (Definitive). There is enough evidence to support a gene-disease association. This gene should be Green at the next review.
Malformations of cortical development v2.116 RAB18 Ivone Leong Gene: rab18 has been classified as Amber List (Moderate Evidence).
Malformations of cortical development v2.115 RAB18 Ivone Leong Phenotypes for gene: RAB18 were changed from Warburg micro syndrome 3, MIM# 614222 to Warburg micro syndrome 3, OMIM:614222
Malformations of cortical development v2.114 NPRL3 Ivone Leong Tag Q4_21_rating tag was added to gene: NPRL3.
Malformations of cortical development v2.114 NPRL3 Ivone Leong Classified gene: NPRL3 as Amber List (moderate evidence)
Malformations of cortical development v2.114 NPRL3 Ivone Leong Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is associated with a phenotype in OMIM but not Gene2Phenotype. There is enough evidence to support a gene-disease association. This gene should be given a Green rating at the next review.
Malformations of cortical development v2.114 NPRL3 Ivone Leong Gene: nprl3 has been classified as Amber List (Moderate Evidence).
Malformations of cortical development v2.113 NPRL3 Ivone Leong Phenotypes for gene: NPRL3 were changed from Epilepsy, familial focal, with variable foci 3 (MIM#617118) to Epilepsy, familial focal, with variable foci 3, OMIM:617118
Malformations of cortical development v2.112 NPRL2 Ivone Leong Penetrance for gene NPRL2 was set from to None
Malformations of cortical development v2.111 NPRL2 Ivone Leong Classified gene: NPRL2 as Amber List (moderate evidence)
Malformations of cortical development v2.111 NPRL2 Ivone Leong Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is associated with a phenotype in OMIM but not Gene2Phenotype. It should be noted that not all patients with variants in this gene has focal cortical dysplasia; however, there is enough evidence to support a gene-disease association. This gene should be rated Green at the next review.
Malformations of cortical development v2.111 NPRL2 Ivone Leong Gene: nprl2 has been classified as Amber List (Moderate Evidence).
Malformations of cortical development v2.110 NPRL2 Ivone Leong Tag Q4_21_rating tag was added to gene: NPRL2.
Malformations of cortical development v2.110 NPRL2 Ivone Leong Added comment: Comment on publications: PMID: 30093711 describes another 2 cases with FCD.
Malformations of cortical development v2.110 NPRL2 Ivone Leong Publications for gene: NPRL2 were set to 29281825; 27173016; 31625153
Malformations of cortical development v2.109 NPRL2 Ivone Leong Phenotypes for gene: NPRL2 were changed from Epilepsy, familial focal, with variable foci 2, MIM# 617116 to Epilepsy, familial focal, with variable foci 2, OMIM:617116
Malformations of cortical development v2.108 GRIN2B Ivone Leong Classified gene: GRIN2B as Amber List (moderate evidence)
Malformations of cortical development v2.108 GRIN2B Ivone Leong Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is associated with a phenotype in OMIM and Gene2Phenotype. There is enough evidence to support a gene-disease association. This gene should be rated Green at the next review.
Malformations of cortical development v2.108 GRIN2B Ivone Leong Gene: grin2b has been classified as Amber List (Moderate Evidence).
Malformations of cortical development v2.107 GRIN2B Ivone Leong Tag Q4_21_rating tag was added to gene: GRIN2B.
Malformations of cortical development v2.107 GRIN2B Ivone Leong Phenotypes for gene: GRIN2B were changed from Mental retardation, autosomal dominant 6, MIM# 613970 to Intellectual developmental disorder, autosomal dominant 6, with or without seizures, OMIM:613970
Malformations of cortical development v2.106 SCN3A Ivone Leong Classified gene: SCN3A as Amber List (moderate evidence)
Malformations of cortical development v2.106 SCN3A Ivone Leong Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is associated with a phenotype in OMIM and Gene2Phenotype (Strong). PMID: 34081427 reports that 31/38 (82%) cases have malformation of cortical development. There is enough evidence to support a gene-disease association. This gene should be rated Green at the next review.
Malformations of cortical development v2.106 SCN3A Ivone Leong Gene: scn3a has been classified as Amber List (Moderate Evidence).
Malformations of cortical development v2.105 SCN3A Ivone Leong Tag Q4_21_rating tag was added to gene: SCN3A.
Malformations of cortical development v2.105 SCN3A Ivone Leong Publications for gene: SCN3A were set to 32515017; 30146301
Malformations of cortical development v2.104 SCN3A Ivone Leong Phenotypes for gene: SCN3A were changed from Polymicrogyria; malformations of cortical development; epilepsy to Polymicrogyria, MONDO:0000087; malformations of cortical development; epilepsy, MONDO:0005027; Developmental and epileptic encephalopathy 62, OMIM:617938
Malformations of cortical development v2.103 ATP1A3 Ivone Leong Phenotypes for gene: ATP1A3 were changed from Polymicrogyria; epilepsy; developmental delay to Polymicrogyria, MONDO:0000087; epilepsy, MONDO:0005027; developmental delay; Developmental and epileptic encephalopathy 99, OMIM:619606
Malformations of cortical development v2.102 ATP1A3 Ivone Leong Classified gene: ATP1A3 as Amber List (moderate evidence)
Malformations of cortical development v2.102 ATP1A3 Ivone Leong Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is associated with a phenotype in OMIM and Gene2Phenotype. PMID:33880529 describes additional cases of patients with variants in ATP1A3 who have polymicrogyria. There is enough evidence to support a gene-disease association. This gene should be rated Green at the next review.
Malformations of cortical development v2.102 ATP1A3 Ivone Leong Gene: atp1a3 has been classified as Amber List (Moderate Evidence).
Malformations of cortical development v2.101 ATP1A3 Ivone Leong Publications for gene: ATP1A3 were set to 33762331
Malformations of cortical development v2.100 ATP1A3 Ivone Leong Tag Q4_21_rating tag was added to gene: ATP1A3.
Malformations of cortical development v2.100 ENO1 Ivone Leong Classified gene: ENO1 as Red List (low evidence)
Malformations of cortical development v2.100 ENO1 Ivone Leong Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is not associated with a phenotype in OMIM or Gene2Phenotype. There is currently not enough evidence to support a gene-disease association. This gene has been given a Red rating.
Malformations of cortical development v2.100 ENO1 Ivone Leong Gene: eno1 has been classified as Red List (Low Evidence).
Malformations of cortical development v2.99 ENO1 Ivone Leong Phenotypes for gene: ENO1 were changed from Polymicrogyria to Polymicrogyria, MONDO:0000087
Malformations of cortical development v2.98 RAB3GAP2 Arina Puzriakova Phenotypes for gene: RAB3GAP2 were changed from Warburg micro syndrome 2, MIM# 614225 to Warburg micro syndrome 2, OMIM:614225
Malformations of cortical development v2.97 MAPK8IP3 Arina Puzriakova Tag Q4_21_rating tag was added to gene: MAPK8IP3.
Malformations of cortical development v2.97 MAPK8IP3 Arina Puzriakova Publications for gene: MAPK8IP3 were set to 30612693
Malformations of cortical development v2.96 MAPK8IP3 Arina Puzriakova Classified gene: MAPK8IP3 as Amber List (moderate evidence)
Malformations of cortical development v2.96 MAPK8IP3 Arina Puzriakova Added comment: Comment on list classification: 18 individuals from 17 families reported with de novo variants in this gene (PMIDs: 30612693; 30945334). Various brain malformations affecting both cerebral and cerebellar structures identified in all except four individuals. Overall there is sufficient evidence to promote this gene to Green at the next GMS panel update.
Malformations of cortical development v2.96 MAPK8IP3 Arina Puzriakova Gene: mapk8ip3 has been classified as Amber List (Moderate Evidence).
Malformations of cortical development v2.95 MAPK8IP3 Arina Puzriakova Phenotypes for gene: MAPK8IP3 were changed from Neurodevelopmental disorder with or without variable brain abnormalities OMIM# 605431 to Neurodevelopmental disorder with or without variable brain abnormalities, OMIM:618443
Malformations of cortical development v2.94 PI4KA Ivone Leong Tag watchlist was removed from gene: PI4KA.
Tag Q4_21_rating tag was added to gene: PI4KA.
Malformations of cortical development v2.94 PI4KA Ivone Leong Publications for gene: PI4KA were set to 25855803
Malformations of cortical development v2.93 PI4KA Ivone Leong edited their review of gene: PI4KA: Added comment: There is now enough evidence to support this gene-disease association. This gene should be rated Green at the next review.

PMID: 25855803. From OMIM: "3 fetuses were all diagnosed in utero with multiple congenital anomalies resulting in the termination of pregnancy between 16 and 34 weeks' gestation. All fetuses had bilateral perisylvian polymicrogyria and cerebellar hypoplasia or dysplasia. One had a small pons. Additional features included severe talipes equinovarus, externally rotated hips, and variable contractures of the limbs or fingers."

PMID:34415322. 10 patients from 10 unrelated families with biallelic varaints in PI4KA. Patients showed a spectrum of severe global neurodevelopmental delay (8/10 moderate to severe ID), hypomyelination, cerebellar hyoplasia (1/10), cerebellar atrophy (5/10), bilateral perisylvian polymicrogyria (1/10), immunological problems (hypogammaglobulinaemia, lymphopaenia, and autoimmune neutorpaenia - 4/10), bowl dysfunction (4/10). Age of onset ranged from newborn to 17 years.

PMID: 34415310. 7 unrelated families. Family 1: Amish. Severe extensive multiple intestinal atresia, IBD and combined immunodeficiency (2/4). Families 3 - 8 all have 1 affected individual, (Turkish, Indian, German and Italian). Global developmental delay (all), ID (severe to mild), cerebellar and/or brainstem anomalies (3/6), spasticity (all), immature gyral pattern (1/6), leukodystrophy (6/6), multiple intestinal atresia (0/6), IBD (3/6), combined immunodeficiency (2/6). Early age of onset.; Changed rating: GREEN; Changed publications to: 25855803, 34415322, 34415310
Malformations of cortical development v2.93 PI4KA Ivone Leong changed review comment from: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is associated with a relevant phenotype in OMIM and Gene2Phenotype. There is currently not enough evidence to support a gene-disease association. This gene has been given an Amber rating.; to: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is associated with a relevant phenotype in OMIM and Gene2Phenotype. There is currently not enough evidence to support a gene-disease association. This gene has been given an Amber rating.
Malformations of cortical development v2.93 TBC1D32 Ivone Leong Tag Q3_21_rating tag was added to gene: TBC1D32.
Malformations of cortical development v2.93 TBC1D32 Ivone Leong Entity copied from Rare multisystem ciliopathy disorders v1.147
Malformations of cortical development v2.93 TBC1D32 Ivone Leong gene: TBC1D32 was added
gene: TBC1D32 was added to Malformations of cortical development. Sources: Radboud University Medical Center, Nijmegen,Expert list,Expert Review Amber
Mode of inheritance for gene: TBC1D32 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TBC1D32 were set to 32573025; 31130284; 32060556; 24285566
Phenotypes for gene: TBC1D32 were set to Orofaciodigital syndrome, MONDO:0015375
Penetrance for gene: TBC1D32 were set to Complete
Malformations of cortical development v2.92 VPS50 Ivone Leong Entity copied from Intellectual disability v3.1322
Malformations of cortical development v2.92 VPS50 Ivone Leong gene: VPS50 was added
gene: VPS50 was added to Malformations of cortical development. Sources: Literature,Expert Review Amber
watchlist tags were added to gene: VPS50.
Mode of inheritance for gene: VPS50 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: VPS50 were set to 34037727
Phenotypes for gene: VPS50 were set to Neonatal cholestatic liver disease; Failure to thrive; Profound global developmental delay; Postnatal microcephaly; Seizures; Abnormality of the corpus callosum
Penetrance for gene: VPS50 were set to Complete
Malformations of cortical development v2.91 TP73 Arina Puzriakova Entity copied from Intellectual disability v3.1295
Malformations of cortical development v2.91 TP73 Arina Puzriakova gene: TP73 was added
gene: TP73 was added to Malformations of cortical development. Sources: Expert list,Expert Review Amber
Q3_21_rating tags were added to gene: TP73.
Mode of inheritance for gene: TP73 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TP73 were set to 31130284; 34077761
Phenotypes for gene: TP73 were set to Ciliary dyskinesia, primary, 47, and lissencephaly, OMIM:619466
Malformations of cortical development v2.90 GRIN1 Sarah Leigh Added comment: Comment on mode of inheritance: Although the MOI could be listed as "both mono and biallelic" in order to agree with the MOI listed in OMIM:138249, this was not done on this panel, as the phenotypes of malformation of cortical development have not been reported with biallelic variants.
Malformations of cortical development v2.90 GRIN1 Sarah Leigh Mode of inheritance for gene: GRIN1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Malformations of cortical development v2.89 GRIN1 Sarah Leigh edited their review of gene: GRIN1: Added comment: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen, although there is a confirmed association with epileptic encephalopathy in Gen2Phen. Nine de novo GRIN1 variants in eleven cases of bilateral polymicrogyria have been reported by Fry et al (PMID: 29365063), analysis of available samples from parents confirmed the de novo occurance of these GRIN1 variants.; Changed rating: GREEN; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Malformations of cortical development v2.89 GRIN1 Sarah Leigh Tag Q3_21_rating tag was added to gene: GRIN1.
Malformations of cortical development v2.89 GRIN1 Sarah Leigh Phenotypes for gene: GRIN1 were changed from Neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal dominant, OMIM:614254 to Neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal dominant OMIM:614254; intellectual disability, autosomal dominant 8 MONDO:0013655
Malformations of cortical development v2.88 GRIN1 Sarah Leigh Publications for gene: GRIN1 were set to 29365063
Malformations of cortical development v2.87 GRIN1 Sarah Leigh Classified gene: GRIN1 as Amber List (moderate evidence)
Malformations of cortical development v2.87 GRIN1 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Malformations of cortical development v2.87 GRIN1 Sarah Leigh Gene: grin1 has been classified as Amber List (Moderate Evidence).
Malformations of cortical development v2.86 GRIN1 Ivone Leong Phenotypes for gene: GRIN1 were changed from Neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal dominant, MIM# 614254 to Neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal dominant, OMIM:614254
Malformations of cortical development v2.85 FAT4 Ivone Leong Tag watchlist tag was added to gene: FAT4.
Malformations of cortical development v2.85 FAT4 Ivone Leong Classified gene: FAT4 as Amber List (moderate evidence)
Malformations of cortical development v2.85 FAT4 Ivone Leong Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is associated with a relevant phenotype in OMIM and Gene2Phenotype. There is currently not enough evidence to support a gene-disease association. This gene has been given an Amber rating.
Malformations of cortical development v2.85 FAT4 Ivone Leong Gene: fat4 has been classified as Amber List (Moderate Evidence).
Malformations of cortical development v2.84 FAT4 Ivone Leong Phenotypes for gene: FAT4 were changed from Van Maldergem syndrome 2, MIM# 615546 to Van Maldergem syndrome 2, OMIM:615546
Malformations of cortical development v2.83 EML1 Arina Puzriakova Publications for gene: EML1 were set to 31710781
Malformations of cortical development v2.82 EML1 Arina Puzriakova Tag Q3_21_rating tag was added to gene: EML1.
Malformations of cortical development v2.82 EML1 Arina Puzriakova Classified gene: EML1 as Amber List (moderate evidence)
Malformations of cortical development v2.82 EML1 Arina Puzriakova Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). EML1 is associated with a relevant phenotype in OMIM (MIM# 600348) but is not yet listed in G2P. Animal models and sufficient number of unrelated cases (>3) with relevant phenotype (periventricular and ribbon-like subcortical heterotopia with polymicrogyria) and variants in this gene to rate as Green at the next GMS panel update.
Malformations of cortical development v2.82 EML1 Arina Puzriakova Gene: eml1 has been classified as Amber List (Moderate Evidence).
Malformations of cortical development v2.81 EML1 Arina Puzriakova Phenotypes for gene: EML1 were changed from Band heterotopia (MIM# 600348) to Band heterotopia, OMIM:600348
Malformations of cortical development v2.80 DEPDC5 Arina Puzriakova Publications for gene: DEPDC5 were set to 31444548
Malformations of cortical development v2.79 DEPDC5 Arina Puzriakova Phenotypes for gene: DEPDC5 were changed from Epilepsy, familial focal, with variable foci 1, OMIM:604364 to Epilepsy, familial focal, with variable foci 1, OMIM:604364; Focal cortical dysplasia
Malformations of cortical development v2.78 DEPDC5 Arina Puzriakova Tag Q3_21_rating tag was added to gene: DEPDC5.
Malformations of cortical development v2.78 DEPDC5 Arina Puzriakova Classified gene: DEPDC5 as Amber List (moderate evidence)
Malformations of cortical development v2.78 DEPDC5 Arina Puzriakova Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). DEPDC5 is associated with a relevant phenotype in OMIM (MIM# 604364) and G2P ('confirmed' disease confidence rating). Sufficient number of unrelated cases (>3) with relevant phenotype (focal cortical dysplasia of variable severity) and variants in this gene to rate as Green at the next GMS panel update.
Malformations of cortical development v2.78 DEPDC5 Arina Puzriakova Gene: depdc5 has been classified as Amber List (Moderate Evidence).
Malformations of cortical development v2.77 DEPDC5 Arina Puzriakova Phenotypes for gene: DEPDC5 were changed from Epilepsy, familial focal, with variable foci 1 (MIM#604364) to Epilepsy, familial focal, with variable foci 1, OMIM:604364
Malformations of cortical development v2.76 DCHS1 Arina Puzriakova changed review comment from: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). DCHS1 is associated with a relevant phenotype in OMIM (MIM# 601390) and G2P ('confirmed' disease confidence rating). Sufficient number of unrelated cases with relevant phenotype and variants in this gene to rate as Green.

Brain MRI typically shows periventricular nodular heterotopia, often with a dysmorphic corpus callosum or simplified gyral pattern, consistent with a neuronal migration defect.; to: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). DCHS1 is associated with a relevant phenotype in OMIM (MIM# 601390) and G2P ('confirmed' disease confidence rating). Sufficient number of unrelated cases (4 patients from 3 families) with relevant phenotype and confirmed variants in this gene to rate as Green.

Brain MRI typically shows periventricular nodular heterotopia, often with a dysmorphic corpus callosum or simplified gyral pattern, consistent with a neuronal migration defect.
Malformations of cortical development v2.76 DCHS1 Arina Puzriakova Publications for gene: DCHS1 were set to 27262615; 22473091
Malformations of cortical development v2.75 DCHS1 Arina Puzriakova Tag Q3_21_rating tag was added to gene: DCHS1.
Malformations of cortical development v2.75 DCHS1 Arina Puzriakova Classified gene: DCHS1 as Amber List (moderate evidence)
Malformations of cortical development v2.75 DCHS1 Arina Puzriakova Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). DCHS1 is associated with a relevant phenotype in OMIM (MIM# 601390) and G2P ('confirmed' disease confidence rating). Sufficient number of unrelated cases with relevant phenotype and variants in this gene to rate as Green.

Brain MRI typically shows periventricular nodular heterotopia, often with a dysmorphic corpus callosum or simplified gyral pattern, consistent with a neuronal migration defect.
Malformations of cortical development v2.75 DCHS1 Arina Puzriakova Gene: dchs1 has been classified as Amber List (Moderate Evidence).
Malformations of cortical development v2.74 DCHS1 Arina Puzriakova Phenotypes for gene: DCHS1 were changed from Van Maldergem syndrome 1, OMIM:601390 to Van Maldergem syndrome 1, OMIM:601390; Periventricular nodular heterotopia
Malformations of cortical development v2.73 DCHS1 Arina Puzriakova Phenotypes for gene: DCHS1 were changed from Van Maldergem syndrome 1 (MIM#601390) to Van Maldergem syndrome 1, OMIM:601390
Malformations of cortical development v2.72 CTNNA2 Arina Puzriakova Tag Q3_21_rating tag was added to gene: CTNNA2.
Malformations of cortical development v2.72 CTNNA2 Arina Puzriakova Classified gene: CTNNA2 as Amber List (moderate evidence)
Malformations of cortical development v2.72 CTNNA2 Arina Puzriakova Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). CTNNA2 is associated with a relevant phenotype in OMIM (MIM# 618174) and G2P ('probable' disease confidence rating). There is sufficient evidence to rate this gene as Green at the next GMS panel update - 13 patients from 3 unrelated families, pachygyria without posterior-anterior gradient or focal dysplasias was common to all.
Malformations of cortical development v2.72 CTNNA2 Arina Puzriakova Gene: ctnna2 has been classified as Amber List (Moderate Evidence).
Malformations of cortical development v2.71 CTNNA2 Arina Puzriakova Phenotypes for gene: CTNNA2 were changed from Cortical dysplasia, complex, with other brain malformations 9, MIM#618174 to Cortical dysplasia, complex, with other brain malformations 9, OMIM:618174
Malformations of cortical development v2.70 CSNK2A1 Arina Puzriakova Classified gene: CSNK2A1 as Green List (high evidence)
Malformations of cortical development v2.70 CSNK2A1 Arina Puzriakova Added comment: Comment on list classification: Three individuals reported by Okur et al., 2016 (PMID: 27048600) displayed cortical abnormalities which meets the threshold for a Green rating. However it should be noted that this is not a common finding and has not been described since the initial report.
Malformations of cortical development v2.70 CSNK2A1 Arina Puzriakova Gene: csnk2a1 has been classified as Green List (High Evidence).
Malformations of cortical development v2.69 CSNK2A1 Arina Puzriakova Publications for gene: CSNK2A1 were set to 27048600
Malformations of cortical development v2.68 CSNK2A1 Arina Puzriakova Phenotypes for gene: CSNK2A1 were changed from 617062 to Okur-Chung neurodevelopmental syndrome, OMIM:617062
Malformations of cortical development v2.67 PEX7 Arina Puzriakova Tag Q3_21_rating tag was added to gene: PEX7.
Tag Q3_21_expert_review tag was added to gene: PEX7.
Malformations of cortical development v2.67 PEX7 Arina Puzriakova commented on gene: PEX7
Malformations of cortical development v2.67 PIDD1 Arina Puzriakova Classified gene: PIDD1 as Amber List (moderate evidence)
Malformations of cortical development v2.67 PIDD1 Arina Puzriakova Gene: pidd1 has been classified as Amber List (Moderate Evidence).
Malformations of cortical development v2.66 PIDD1 Arina Puzriakova gene: PIDD1 was added
gene: PIDD1 was added to Malformations of cortical development. Sources: Literature
Q3_21_rating tags were added to gene: PIDD1.
Mode of inheritance for gene: PIDD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PIDD1 were set to 33414379; 34163010
Phenotypes for gene: PIDD1 were set to Intellectual disability; Pachygyria; Lissencephaly; Seizures
Review for gene: PIDD1 was set to GREEN
Added comment: At least 9 distinct biallelic variants have been identified in 26 individuals from 11 families. All affected individuals had DD and variable degree of ID (mild to severe) and all those that had brain imaging exhibited cortical abnormalities, particularly pachygyria/lissencephaly and corpus callosum anomalies. Seizures were recorded in 9 patients (6 families).

Overall there is are sufficient unrelated cases with relevant phenotype and biallelic variants in this gene to rate as Green on this panel.
Sources: Literature
Malformations of cortical development v2.65 CRADD Arina Puzriakova Phenotypes for gene: CRADD were changed from Mental retardation, autosomal recessive 34, with variant lissencephaly, MIM# 614499 to Mental retardation, autosomal recessive 34, with variant lissencephaly, OMIM:614499
Malformations of cortical development v2.64 CRADD Arina Puzriakova Publications for gene: CRADD were set to 27773430
Malformations of cortical development v2.63 CRADD Arina Puzriakova Classified gene: CRADD as Amber List (moderate evidence)
Malformations of cortical development v2.63 CRADD Arina Puzriakova Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). Brain phenotypes include megalencephaly with variable lissencephaly/pachygyria. Sufficient number of unrelated cases (>3) to rate as Green on this panel.
Malformations of cortical development v2.63 CRADD Arina Puzriakova Gene: cradd has been classified as Amber List (Moderate Evidence).
Malformations of cortical development v2.62 CRADD Arina Puzriakova Tag Q3_21_rating tag was added to gene: CRADD.
Malformations of cortical development v2.62 CDK13 Arina Puzriakova reviewed gene: CDK13: Rating: GREEN; Mode of pathogenicity: None; Publications: 27479907, 29021403; Phenotypes: Congenital heart defects, dysmorphic facial features, and intellectual developmental disorder, OMIM:617360; Mode of inheritance: None
Malformations of cortical development v2.62 ARF1 Arina Puzriakova Added comment: Comment on publications: Gana et al., 2021 (PMID: 34353862) - additional family identified with a 5-year-old girl who inherited a heterozygous nonsense variant in the ARF1 gene (c.234G>A; p.Trp78Ter) from her father. Both displayed periventricular nodular heterotopia on brain MRI but with milder clinical expression in the father.
Malformations of cortical development v2.62 ARF1 Arina Puzriakova Publications for gene: ARF1 were set to 28868155
Malformations of cortical development v2.61 PI4KA Ivone Leong Tag watchlist tag was added to gene: PI4KA.
Malformations of cortical development v2.61 PI4KA Ivone Leong Classified gene: PI4KA as Amber List (moderate evidence)
Malformations of cortical development v2.61 PI4KA Ivone Leong Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is associated with a relevant phenotype in OMIM and Gene2Phenotype. There is currently not enough evidence to support a gene-disease association. This gene has been given an Amber rating.
Malformations of cortical development v2.61 PI4KA Ivone Leong Gene: pi4ka has been classified as Amber List (Moderate Evidence).
Malformations of cortical development v2.60 PI4KA Ivone Leong Phenotypes for gene: PI4KA were changed from Polymicrogyria, perisylvian, with cerebellar hypoplasia and arthrogryposis, MIM# 616531 to Polymicrogyria, perisylvian, with cerebellar hypoplasia and arthrogryposis, OMIM:616531
Malformations of cortical development v2.59 B4GAT1 Ivone Leong Tag Q3_21_rating tag was added to gene: B4GAT1.
Malformations of cortical development v2.59 B4GAT1 Ivone Leong Classified gene: B4GAT1 as Amber List (moderate evidence)
Malformations of cortical development v2.59 B4GAT1 Ivone Leong Added comment: Comment on list classification: This gene is associated with a relevant phenotype in OMIM but not in Gene2Phenotype. There is enough evidence to support a gene-disease association. This gene should be rated Green at the next review.
Malformations of cortical development v2.59 B4GAT1 Ivone Leong Gene: b4gat1 has been classified as Amber List (Moderate Evidence).
Malformations of cortical development v2.58 B4GAT1 Ivone Leong Publications for gene: B4GAT1 were set to 23359570; 23877401; 23359570; 23217742
Malformations of cortical development v2.57 B4GAT1 Ivone Leong Phenotypes for gene: B4GAT1 were changed from Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 13 615287 to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 13, OMIM:615287
Malformations of cortical development v2.56 B4GAT1 Ivone Leong Publications for gene: B4GAT1 were set to 23359570
Malformations of cortical development v2.55 ARF1 Ivone Leong Tag Q3_21_rating tag was added to gene: ARF1.
Malformations of cortical development v2.55 ARF1 Ivone Leong Classified gene: ARF1 as Amber List (moderate evidence)
Malformations of cortical development v2.55 ARF1 Ivone Leong Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is associated with a relevant phenotype in OMIM and Gene2Phenotype. There is enough evidence to support a gene-disease association. This gene should be rated Green at the next review.
Malformations of cortical development v2.55 ARF1 Ivone Leong Gene: arf1 has been classified as Amber List (Moderate Evidence).
Malformations of cortical development v2.54 ARF1 Ivone Leong Phenotypes for gene: ARF1 were changed from Periventricular nodular heterotopia 8, MIM# 618185 to Periventricular nodular heterotopia 8, OMIM:618185
Malformations of cortical development v2.53 MCF2 Ivone Leong Classified gene: MCF2 as Red List (low evidence)
Malformations of cortical development v2.53 MCF2 Ivone Leong Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is not associated with a phenotype in OMIM or Gene2Phenotype. There is currently not enough evidence to support a gene-disease association. This gene has been given a Red rating.
Malformations of cortical development v2.53 MCF2 Ivone Leong Gene: mcf2 has been classified as Red List (Low Evidence).
Malformations of cortical development v2.52 MCF2 Ivone Leong Phenotypes for gene: MCF2 were changed from Perisylvian polymicrogyria to Perisylvian polymicrogyria; bilateral perisylvian polymicrogyria, MONDO:0020340
Malformations of cortical development v2.51 EMX2 Ivone Leong Phenotypes for gene: EMX2 were changed from Schizencephaly, 269160 to Schizencephaly, OMIM:269160
Malformations of cortical development v2.50 EMX2 Ivone Leong Publications for gene: EMX2 were set to 8528262; 9359037
Malformations of cortical development v2.49 FIG4 Sarah Leigh Classified gene: FIG4 as Amber List (moderate evidence)
Malformations of cortical development v2.49 FIG4 Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM, but not associated with ?Polymicrogyria, bilateral temporooccipital OMIM:612691 in Gen2Phen. A single missense variant has been reported in a large consanguineous Moroccan family, supportive functional studies were also reported (PMID: 24598713).
Malformations of cortical development v2.49 FIG4 Sarah Leigh Gene: fig4 has been classified as Amber List (Moderate Evidence).
Malformations of cortical development v2.48 FIG4 Sarah Leigh Added comment: Comment on phenotypes: FIG4 variants also are associated with Amyotrophic lateral sclerosis 11 OMIM:612577; Charcot-Marie-Tooth disease, type 4J OMIM:611228 and Yunis-Varon syndrome OMIM:216340, but these phenotypes are not appropriate for this panel.
Malformations of cortical development v2.48 FIG4 Sarah Leigh Phenotypes for gene: FIG4 were changed from ?Polymicrogyria, bilateral temporooccipital OMIM:612691; bilateral parasagittal parieto-occipital polymicrogyria MONDO:0012986 to ?Polymicrogyria, bilateral temporooccipital OMIM:612691; bilateral parasagittal parieto-occipital polymicrogyria MONDO:0012986
Malformations of cortical development v2.47 FIG4 Sarah Leigh Phenotypes for gene: FIG4 were changed from Polymicrogyria with epilepsy MIM# 612691 to ?Polymicrogyria, bilateral temporooccipital OMIM:612691; bilateral parasagittal parieto-occipital polymicrogyria MONDO:0012986
Malformations of cortical development v2.46 DPYSL5 Ivone Leong Entity copied from Intellectual disability v3.1214
Malformations of cortical development v2.46 DPYSL5 Ivone Leong gene: DPYSL5 was added
gene: DPYSL5 was added to Malformations of cortical development. Sources: Expert Review Amber,Literature
Q3_21_rating tags were added to gene: DPYSL5.
Mode of inheritance for gene: DPYSL5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DPYSL5 were set to 33894126
Phenotypes for gene: DPYSL5 were set to Neurodevelopmental disorder with corpus callosum agenesis and cerebellar abnormalities
Malformations of cortical development v2.45 CEP85L Rachel Challis reviewed gene: CEP85L: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID 32097629, 32097630; Phenotypes: Intellectual disability, epilepsy, lissencephaly; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Malformations of cortical development v2.45 FLNA Arina Puzriakova Phenotypes for gene: FLNA were changed from Periventricular Heterotopia 300049; Melnick-Needles syndrome 309350; Otopalatodigital syndrome, type I 311300; Otopalatodigital syndrome, type II 304120 to Heterotopia, periventricular, 1, OMIM:300049
Malformations of cortical development v2.44 ATP1A3 Zornitza Stark gene: ATP1A3 was added
gene: ATP1A3 was added to Malformations of cortical development. Sources: Literature
Mode of inheritance for gene: ATP1A3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ATP1A3 were set to 33762331
Phenotypes for gene: ATP1A3 were set to Polymicrogyria; epilepsy; developmental delay
Review for gene: ATP1A3 was set to GREEN
gene: ATP1A3 was marked as current diagnostic
Added comment: Eight individuals with de novo variants reported and a phenotype distinct from those previously reported in association with this gene.
Sources: Literature
Malformations of cortical development v2.44 SLC35A2 Zornitza Stark changed review comment from: >20 individuals reported. However note variants were identified on deep sequencing of affected tissue, and are somatic.
Sources: Literature; to: >20 individuals reported. However note variants were identified on deep sequencing of affected tissue, and are somatic. Rated as Amber as uncertain whether panel only caters to germline sequencing.
Sources: Literature
Malformations of cortical development v2.44 SLC35A2 Zornitza Stark gene: SLC35A2 was added
gene: SLC35A2 was added to Malformations of cortical development. Sources: Literature
Mode of inheritance for gene: SLC35A2 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: SLC35A2 were set to 33407896
Phenotypes for gene: SLC35A2 were set to Mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy (MOGHE)
Review for gene: SLC35A2 was set to AMBER
Added comment: >20 individuals reported. However note variants were identified on deep sequencing of affected tissue, and are somatic.
Sources: Literature
Malformations of cortical development v2.44 ENO1 Zornitza Stark gene: ENO1 was added
gene: ENO1 was added to Malformations of cortical development. Sources: Literature
Mode of inheritance for gene: ENO1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ENO1 were set to 32488097
Phenotypes for gene: ENO1 were set to Polymicrogyria
Review for gene: ENO1 was set to RED
Added comment: ENO1 identified as a polymicrogyria candidate gene from the smallest case of 1p36 duplication reported to date, in a 35yo F (onset at 8mo) presenting intellectual disability, microcephaly, epilepsy and perisylvian polymicrogyria. The duplication only encompassed 2 genes, ENO1 and RERE, and gene expression analysis performed using the patient cells revealed reduced expression, mimicking haploinsufficiency. Eno1 inactivation in rats was shown to cause a brain development defect though note variants in RERE also cause a neurodevelopmental phenotype.
Sources: Literature
Malformations of cortical development v2.44 KATNB1 Arina Puzriakova Phenotypes for gene: KATNB1 were changed from Lissencephaly 6, with microcephaly 616212 to Lissencephaly 6, with microcephaly, OMIM:616212, MONDO:0014534
Malformations of cortical development v2.43 TMX2 Arina Puzriakova Phenotypes for gene: TMX2 were changed from Neurodevelopmental disorder with microcephaly, cortical malformations, and spasticity 618730 to Neurodevelopmental disorder with microcephaly, cortical malformations, and spasticity, OMIM:618730; Neurodevelopmental disorder with microcephaly, cortical malformations, and spasticity, MONDO:0032887
Malformations of cortical development v2.42 APC2 Sarah Leigh Publications for gene: APC2 were set to 31585108
Malformations of cortical development v2.41 APC2 Sarah Leigh Phenotypes for gene: APC2 were changed from Cortical dysplasia, complex, with other brain malformations 10, MIM#618677 to Cortical dysplasia, complex, with other brain malformations 10 OMIM:618677
Malformations of cortical development v2.40 APC2 Sarah Leigh Classified gene: APC2 as Amber List (moderate evidence)
Malformations of cortical development v2.40 APC2 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Malformations of cortical development v2.40 APC2 Sarah Leigh Gene: apc2 has been classified as Amber List (Moderate Evidence).
Malformations of cortical development v2.39 APC2 Sarah Leigh Tag for-review tag was added to gene: APC2.
Malformations of cortical development v2.39 APC2 Sarah Leigh reviewed gene: APC2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Malformations of cortical development v2.39 SNAP29 Arina Puzriakova Phenotypes for gene: SNAP29 were changed from Cerebral dysgenesis, neuropathy, ichthyosis, and palmoplantar keratoderma syndrome (MIM#609528) to Cerebral dysgenesis, neuropathy, ichthyosis, and palmoplantar keratoderma syndrome, OMIM:609528; CEDNIK syndrome, MONDO:0012290
Malformations of cortical development v2.38 SNAP29 Arina Puzriakova Publications for gene: SNAP29 were set to 29051910; 21073448; 30793783
Malformations of cortical development v2.37 SNAP29 Arina Puzriakova Tag for-review tag was added to gene: SNAP29.
Malformations of cortical development v2.37 SNAP29 Arina Puzriakova Classified gene: SNAP29 as Amber List (moderate evidence)
Malformations of cortical development v2.37 SNAP29 Arina Puzriakova Added comment: Comment on list classification: New gene added by Zornitza Stark. Cerebral dysgenesis is a universal feature among patients with CEDNIK syndrome caused by biallelic variants in the SNAP29 gene. Reported cerebral abnormalities of various degrees include absence of corpus callosum, cortical dysplasia, pachygyria and polymicrogyria.

There is sufficient evidence to promote SNAP29 to Green at the next GMS panel update (added 'for-review' tag)
Malformations of cortical development v2.37 SNAP29 Arina Puzriakova Gene: snap29 has been classified as Amber List (Moderate Evidence).
Malformations of cortical development v2.36 VLDLR Sarah Leigh edited their review of gene: VLDLR: Added comment: There is enough evidence for this gene to be rated GREEN at the next major review.; Changed rating: GREEN
Malformations of cortical development v2.36 VLDLR Sarah Leigh Classified gene: VLDLR as Amber List (moderate evidence)
Malformations of cortical development v2.36 VLDLR Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least sic variants reported six unrelated cases, in which cerebellar hypoplasia was evident in five cases and two of these had cerebral gyral simplification.
Malformations of cortical development v2.36 VLDLR Sarah Leigh Gene: vldlr has been classified as Amber List (Moderate Evidence).
Malformations of cortical development v2.35 VLDLR Sarah Leigh Tag for-review tag was added to gene: VLDLR.
Malformations of cortical development v2.35 VLDLR Sarah Leigh Phenotypes for gene: VLDLR were changed from Cerebellar hypoplasia and mental retardation with or without quadrupedal locomotion 1 (MIM#224050) to Cerebellar hypoplasia and mental retardation with or without quadrupedal locomotion 1 OMIM:224050
Malformations of cortical development v2.34 LAMA2 Sarah Leigh edited their review of gene: LAMA2: Added comment: There is enough evidence for this gene to be rated GREEN at the next major review.; Changed rating: GREEN
Malformations of cortical development v2.34 LAMA2 Sarah Leigh Tag for-review tag was added to gene: LAMA2.
Malformations of cortical development v2.34 LAMA2 Sarah Leigh Classified gene: LAMA2 as Amber List (moderate evidence)
Malformations of cortical development v2.34 LAMA2 Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. Numerous variants reported as biallelic in Muscular dystrophy, congenital, merosin deficient or partially deficient OMIM:607855, with over three cases exhibiting occipital agyria / polymicrogyria.
Malformations of cortical development v2.34 LAMA2 Sarah Leigh Gene: lama2 has been classified as Amber List (Moderate Evidence).
Malformations of cortical development v2.33 LAMA2 Sarah Leigh Publications for gene: LAMA2 were set to 20207543; 18406646
Malformations of cortical development v2.32 LAMA2 Sarah Leigh Phenotypes for gene: LAMA2 were changed from Muscular dystrophy, congenital, merosin deficient or partially deficient, MIM# 607855 to Muscular dystrophy, congenital, merosin deficient or partially deficient OMIM:607855
Malformations of cortical development v2.31 CASK Sarah Leigh Tag for-review tag was added to gene: CASK.
Malformations of cortical development v2.31 CASK Sarah Leigh edited their review of gene: CASK: Added comment: There is enough evidence for this gene to be rated GREEN at the next major review.; Changed rating: GREEN
Malformations of cortical development v2.31 CASK Sarah Leigh Classified gene: CASK as Amber List (moderate evidence)
Malformations of cortical development v2.31 CASK Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. Numerous variants and cases reported.
Malformations of cortical development v2.31 CASK Sarah Leigh Gene: cask has been classified as Amber List (Moderate Evidence).
Malformations of cortical development v2.30 CASK Sarah Leigh Publications for gene: CASK were set to 21954287; 20595373
Malformations of cortical development v2.29 CASK Sarah Leigh Phenotypes for gene: CASK were changed from Gyral simplification to Mental retardation and microcephaly with pontine and cerebellar hypoplasia OMIM:300749
Malformations of cortical development v2.28 CASK Sarah Leigh Publications for gene: CASK were set to PMID: 21954287, 20595373
Malformations of cortical development v2.27 MN1 Arina Puzriakova Phenotypes for gene: MN1 were changed from CEBALID syndrome, 618774 to CEBALID syndrome, OMIM:618774; CEBALID syndrome, MONDO:0032908
Malformations of cortical development v2.26 ATP1A2 Arina Puzriakova Publications for gene: ATP1A2 were set to 31608932
Malformations of cortical development v2.25 ATP1A2 Arina Puzriakova changed review comment from: Comment on list classification: New gene added by Zornitza Stark. At least 4 unrelated families with multiple congenital abnormalities and different homozygous truncating variants in the ATP1A2 gene. All affected fetuses display a common cerebral phenotype with multiple cortical malformations and polymicrogyria (PMIDs: 30690204 and 316089320)

Rating Amber but there is sufficient evidence to promote to Green at the next GMS panel update (added 'for-review' tag); to: Comment on list classification: New gene added by Zornitza Stark. At least 4 unrelated families with multiple congenital abnormalities and different homozygous truncating variants in the ATP1A2 gene. All affected fetuses display a common cerebral phenotype with multiple cortical malformations and polymicrogyria (PMIDs: 30690204 and 31608932)

Rating Amber but there is sufficient evidence to promote to Green at the next GMS panel update (added 'for-review' tag)
Malformations of cortical development v2.25 ATP1A2 Arina Puzriakova Classified gene: ATP1A2 as Amber List (moderate evidence)
Malformations of cortical development v2.25 ATP1A2 Arina Puzriakova Added comment: Comment on list classification: New gene added by Zornitza Stark. At least 4 unrelated families with multiple congenital abnormalities and different homozygous truncating variants in the ATP1A2 gene. All affected fetuses display a common cerebral phenotype with multiple cortical malformations and polymicrogyria (PMIDs: 30690204 and 316089320)

Rating Amber but there is sufficient evidence to promote to Green at the next GMS panel update (added 'for-review' tag)
Malformations of cortical development v2.25 ATP1A2 Arina Puzriakova Gene: atp1a2 has been classified as Amber List (Moderate Evidence).
Malformations of cortical development v2.24 ATP1A2 Arina Puzriakova Tag for-review tag was added to gene: ATP1A2.
Malformations of cortical development v2.24 CASK Ian Berry gene: CASK was added
gene: CASK was added to Malformations of cortical development. Sources: NHS GMS
Mode of inheritance for gene: CASK was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: CASK were set to PMID: 21954287, 20595373
Phenotypes for gene: CASK were set to Gyral simplification
Review for gene: CASK was set to GREEN
gene: CASK was marked as current diagnostic
Added comment: Multiple publications reporting a subset of patients with simplified gyral pattern, in addition to the more recognisable features of cerebellar hypoplasia and microcephaly.
Sources: NHS GMS
Malformations of cortical development v2.24 LAMA2 Ian Berry reviewed gene: LAMA2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Malformations of cortical development v2.24 VLDLR Ian Berry reviewed gene: VLDLR: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 16174313, 6080122; Phenotypes: Gyral simplification; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Malformations of cortical development v2.24 TUBB2A Arina Puzriakova Phenotypes for gene: TUBB2A were changed from Cortical dysplasia, complex, with other brain malformations 5 615763 to Cortical dysplasia, complex, with other brain malformations 5, OMIM:615763; Complex cortical dysplasia with other brain malformations 5, MONDO:0014337
Malformations of cortical development v2.23 TUBB2A Arina Puzriakova Publications for gene: TUBB2A were set to 24702957
Malformations of cortical development v2.22 H3F3A Arina Puzriakova commented on gene: H3F3A: Added new-gene-name tag, new approved HGNC gene symbol for H3F3A is H3-3A
Malformations of cortical development v2.22 H3F3A Arina Puzriakova Classified gene: H3F3A as Amber List (moderate evidence)
Malformations of cortical development v2.22 H3F3A Arina Puzriakova Added comment: Comment on list classification: New gene added as Amber but there is sufficient evidence to promote to Green at the next GMS panel update (added 'for-review' tag)
Malformations of cortical development v2.22 H3F3A Arina Puzriakova Gene: h3f3a has been classified as Amber List (Moderate Evidence).
Malformations of cortical development v2.21 H3F3A Arina Puzriakova gene: H3F3A was added
gene: H3F3A was added to Malformations of cortical development. Sources: Literature
new-gene-name, for-review tags were added to gene: H3F3A.
Mode of inheritance for gene: H3F3A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: H3F3A were set to 31942419; 33268356
Phenotypes for gene: H3F3A were set to Developmental delay; Intellectual disability; Neurodegeneration; Epilepsy; Facial dysmorphism; Congenital anomalies
Review for gene: H3F3A was set to GREEN
Added comment: Currently not associated with any phenotype in OMIM, but is listed in Gene2Phenotype with a 'confirmed' disease confidence rating for 'Craniofacial with neurodevelopment disorders'.

- PMID: 31942419 (2019) - De novo missense variant identified by trio exome sequencing in a girl with secondary microcephaly, severe DD and ID, growth retardation and dysmorphic features. Brain MRI demonstrated hypoplasia of corpus callosum and cerebellum as well as thin layer of frontal and parietal periventricular gliosis. No functional analyses of the variant or patient cells were performed.

- PMID: 33268356 (2020) - De novo missense variants identified in 33 unrelated individuals with a shared phenotype of GDD/ID, usually severe and often progressive, with mostly minor congenital anomalies. 23/28 patients showed abnormalities on brain MRI including hypoplasia/agenesis of the corpus collosum (9), cortical atrophy (6) and impaired myelination (5). Variable seizure phenotypes were reported in 17/33 cases, all early-onset where specified, mostly during infancy (latest onset at 14 years of age).
Sources: Literature
Malformations of cortical development v2.20 CEP85L Arina Puzriakova Phenotypes for gene: CEP85L were changed from Lissencephaly, posterior predominant to Lissencephaly 10, OMIM:618873; Lissencephaly 10, MONDO:0030031
Malformations of cortical development v2.19 CEP85L Arina Puzriakova Publications for gene: CEP85L were set to 32097630
Malformations of cortical development v2.18 CEP85L Arina Puzriakova Tag for-review tag was added to gene: CEP85L.
Malformations of cortical development v2.18 CEP85L Arina Puzriakova Classified gene: CEP85L as Amber List (moderate evidence)
Malformations of cortical development v2.18 CEP85L Arina Puzriakova Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). There is sufficient evidence to rate this gene Green at the next GMS panel update (added 'for-review' tag).

At least 13 patients from 9 unrelated families with lissencephaly and heterozygous variants in the CEP85L gene. Mouse model supports a role in neuronal migration. Gene-disease association also included in OMIM.
Malformations of cortical development v2.18 CEP85L Arina Puzriakova Gene: cep85l has been classified as Amber List (Moderate Evidence).
Malformations of cortical development v2.17 CDH2 Arina Puzriakova changed review comment from: 2 papers (PMID: 31585109 and 31650526) describing 13 unrelated individuals with a neurodevelopmental disorder and variants in the CDH2 gene. Clinical features include GDD/ID (10/12), brain malformations - particularly agenesis of corpus callosum (11/13), cardiovascular abnormalities (9/13), and various eye abnormalities (11/13).

Cdh2 knockout in mice is embryonically lethal. Conditional inactivation of Cdh2 in the cerebral cortex leads to cortical disorganisation and CCA similar to the human phenotypes (PMIDs: 9015265, 17222817).
Sources: Literature; to: Associated with relevant phenotype in OMIM, and is a 'probable' gene for 'Syndromic Neurodevelopmental Disorder with Corpus Collosum, Axon, Cardiac, Ocular, and Genital Defects' in Gene2Phenotype.

2 papers (PMID: 31585109 and 31650526) describing 13 unrelated individuals with a neurodevelopmental disorder and variants in the CDH2 gene. Clinical features include GDD/ID (10/12), brain malformations - particularly agenesis of corpus callosum (11/13), cardiovascular abnormalities (9/13), and various eye abnormalities (11/13).

Cdh2 knockout in mice is embryonically lethal. Conditional inactivation of Cdh2 in the cerebral cortex leads to cortical disorganisation and CCA similar to the human phenotypes (PMIDs: 9015265, 17222817).
Sources: Literature
Malformations of cortical development v2.17 CDH2 Arina Puzriakova Classified gene: CDH2 as Amber List (moderate evidence)
Malformations of cortical development v2.17 CDH2 Arina Puzriakova Added comment: Comment on list classification: There is sufficient evidence to rate this gene Green at the next GMS panel update (added 'for-review' tag)
Malformations of cortical development v2.17 CDH2 Arina Puzriakova Gene: cdh2 has been classified as Amber List (Moderate Evidence).
Malformations of cortical development v2.16 CDH2 Arina Puzriakova changed review comment from: 2 papers (PMID: 31585109 and 31650526) describing 13 unrelated individuals with a neurodevelopmental disorder and variants in the CDH2 gene. Clinical features include GDD/ID (10/12), brain malformations - particularly agenesis of corpus callosum (11/13), cardiovascular abnormalities (9/13), and various eye abnormalities (11/13).

Cdh2 knockout in mice is embryonically lethal. Conditional inactivation of Cdh2 in the cerebral cortex leads to cortical disorganization and CCA similar to the human phenotypes (PMIDs cited: 9015265, 17222817). Other animal studies (mouse, zebrafish, chicken, dog, etc) are also cited to link with specific defects.
Sources: Literature; to: 2 papers (PMID: 31585109 and 31650526) describing 13 unrelated individuals with a neurodevelopmental disorder and variants in the CDH2 gene. Clinical features include GDD/ID (10/12), brain malformations - particularly agenesis of corpus callosum (11/13), cardiovascular abnormalities (9/13), and various eye abnormalities (11/13).

Cdh2 knockout in mice is embryonically lethal. Conditional inactivation of Cdh2 in the cerebral cortex leads to cortical disorganisation and CCA similar to the human phenotypes (PMIDs: 9015265, 17222817).
Sources: Literature
Malformations of cortical development v2.16 CDH2 Arina Puzriakova gene: CDH2 was added
gene: CDH2 was added to Malformations of cortical development. Sources: Literature
for-review tags were added to gene: CDH2.
Mode of inheritance for gene: CDH2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CDH2 were set to 31585109; 31650526
Phenotypes for gene: CDH2 were set to Agenesis of corpus callosum, cardiac, ocular, and genital syndrome, OMIM:618929; Agenesis of corpus callosum, cardiac, ocular, and genital syndrome, MONDO:0030065
Review for gene: CDH2 was set to GREEN
Added comment: 2 papers (PMID: 31585109 and 31650526) describing 13 unrelated individuals with a neurodevelopmental disorder and variants in the CDH2 gene. Clinical features include GDD/ID (10/12), brain malformations - particularly agenesis of corpus callosum (11/13), cardiovascular abnormalities (9/13), and various eye abnormalities (11/13).

Cdh2 knockout in mice is embryonically lethal. Conditional inactivation of Cdh2 in the cerebral cortex leads to cortical disorganization and CCA similar to the human phenotypes (PMIDs cited: 9015265, 17222817). Other animal studies (mouse, zebrafish, chicken, dog, etc) are also cited to link with specific defects.
Sources: Literature
Malformations of cortical development v2.15 MAP1B Arina Puzriakova Classified gene: MAP1B as Amber List (moderate evidence)
Malformations of cortical development v2.15 MAP1B Arina Puzriakova Added comment: Comment on list classification: There is sufficient evidence to rate this gene Green at the next GMS panel update (added 'for-review' tag). Multiple unrelated families with different variants in the MAP1B gene and brain malformations, particularly PVNH
Malformations of cortical development v2.15 MAP1B Arina Puzriakova Gene: map1b has been classified as Amber List (Moderate Evidence).
Malformations of cortical development v2.14 MAP1B Arina Puzriakova Tag for-review tag was added to gene: MAP1B.
Malformations of cortical development v2.14 MAP1B Arina Puzriakova reviewed gene: MAP1B: Rating: GREEN; Mode of pathogenicity: None; Publications: 30150678, 29738522, 31317654; Phenotypes: Periventricular nodular heterotopia 9, 618918; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Malformations of cortical development v2.14 TMX2 Arina Puzriakova Classified gene: TMX2 as Amber List (moderate evidence)
Malformations of cortical development v2.14 TMX2 Arina Puzriakova Added comment: Comment on list classification: Changed rating to Amber so that Green genes on this panel reflect the NHS signed-off version. This will be reviewed at the next GMS panel update (added 'for-review' tag).
Malformations of cortical development v2.14 TMX2 Arina Puzriakova Gene: tmx2 has been classified as Amber List (Moderate Evidence).
Malformations of cortical development v2.13 TMX2 Arina Puzriakova Tag for-review tag was added to gene: TMX2.
Malformations of cortical development v2.13 TMX2 Zornitza Stark reviewed gene: TMX2: Rating: AMBER; Mode of pathogenicity: None; Publications: 31735293, 31586943; Phenotypes: Neurodevelopmental disorder with microcephaly, cortical malformations, and spasticity MIM#618730; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Malformations of cortical development v2.13 SNAP29 Zornitza Stark gene: SNAP29 was added
gene: SNAP29 was added to Malformations of cortical development. Sources: Expert list
Mode of inheritance for gene: SNAP29 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SNAP29 were set to 29051910; 21073448; 30793783
Phenotypes for gene: SNAP29 were set to Cerebral dysgenesis, neuropathy, ichthyosis, and palmoplantar keratoderma syndrome (MIM#609528)
Review for gene: SNAP29 was set to GREEN
gene: SNAP29 was marked as current diagnostic
Added comment: Associated with CEDNIK syndrome. Both pachygyria and polymicrogyria, and additionally dysgenesis of the corpus callosum, are reported in multiple patients from unrelated families with pathogenic variants in this gene (at least 5 patients from 3 families with both pachygyria and polymicrogyria, and at least 5 patients from 3 families with polymicrogyria alone (PMID: 29051910, 30793783)).
Sources: Expert list
Malformations of cortical development v2.13 SCN3A Zornitza Stark gene: SCN3A was added
gene: SCN3A was added to Malformations of cortical development. Sources: Expert list
Mode of inheritance for gene: SCN3A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SCN3A were set to 32515017; 30146301
Phenotypes for gene: SCN3A were set to Polymicrogyria; malformations of cortical development; epilepsy
Review for gene: SCN3A was set to GREEN
gene: SCN3A was marked as current diagnostic
Added comment: Six unrelated families reported with prominent speech and oral motor dysfunction but no epilepsy, some multiplex in PMID: 30146301. Additionally malformations of cortical development reported in ~75% of a cohort of 22 individuals with a broader neurodevelomental phenotype, including epilepsy, PMID: 32515017
Sources: Expert list
Malformations of cortical development v2.13 RAB3GAP2 Zornitza Stark gene: RAB3GAP2 was added
gene: RAB3GAP2 was added to Malformations of cortical development. Sources: Expert list
Mode of inheritance for gene: RAB3GAP2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RAB3GAP2 were set to 23420520; 20967465
Phenotypes for gene: RAB3GAP2 were set to Warburg micro syndrome 2, MIM# 614225
Review for gene: RAB3GAP2 was set to GREEN
gene: RAB3GAP2 was marked as current diagnostic
Added comment: Polymicrogyria is a well described phenotypic feature in Micro syndrome caused by variants in RAB3GAP2 and other genes.

PMID: 23420520 – at least 3 unrelated families with polymicrogyria
PMID: 20967465 - single proband with polymicrogyria
Sources: Expert list
Malformations of cortical development v2.13 RAB3GAP1 Zornitza Stark gene: RAB3GAP1 was added
gene: RAB3GAP1 was added to Malformations of cortical development. Sources: Expert list
Mode of inheritance for gene: RAB3GAP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RAB3GAP1 were set to 23420520
Phenotypes for gene: RAB3GAP1 were set to Warburg micro syndrome 1, MIM# 600118
Review for gene: RAB3GAP1 was set to GREEN
gene: RAB3GAP1 was marked as current diagnostic
Added comment: Polymicrogyria is a well described phenotypic feature of Micro syndrome, caused by RAB3GAP1 and other genes.

PMID: 23420520 - at least 4 unrelated families with polymicrogyria
Sources: Expert list
Malformations of cortical development v2.13 RAB18 Zornitza Stark gene: RAB18 was added
gene: RAB18 was added to Malformations of cortical development. Sources: Expert list
Mode of inheritance for gene: RAB18 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RAB18 were set to 21473985; 23420520
Phenotypes for gene: RAB18 were set to Warburg micro syndrome 3, MIM# 614222
Review for gene: RAB18 was set to GREEN
Added comment: Polymicrogyria is a well described phenotypic feature in Micro syndrome, caused by RAB18 and other genes.

PMID: 21473985 – two unrelated families with polymicrogyria
PMID: 23420520 – one proband with polymicrogyria
Sources: Expert list
Malformations of cortical development v2.13 PTEN Zornitza Stark gene: PTEN was added
gene: PTEN was added to Malformations of cortical development. Sources: Expert list
Mode of inheritance for gene: PTEN was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PTEN were set to 32162846
Phenotypes for gene: PTEN were set to Cowden syndrome 1 158350; Lhermitte-Duclos syndrome 158350; Macrocephaly/autism syndrome 605309
Review for gene: PTEN was set to GREEN
gene: PTEN was marked as current diagnostic
Added comment: PMID: 32162846 - 4 unrelated individuals with PTEN variants with polymicrogyria
Sources: Expert list
Malformations of cortical development v2.13 PI4KA Zornitza Stark gene: PI4KA was added
gene: PI4KA was added to Malformations of cortical development. Sources: Expert list
Mode of inheritance for gene: PI4KA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PI4KA were set to 25855803
Phenotypes for gene: PI4KA were set to Polymicrogyria, perisylvian, with cerebellar hypoplasia and arthrogryposis, MIM# 616531
Review for gene: PI4KA was set to AMBER
Added comment: One family reported, we are aware of additional cases.
Sources: Expert list
Malformations of cortical development v2.13 NPRL3 Zornitza Stark gene: NPRL3 was added
gene: NPRL3 was added to Malformations of cortical development. Sources: Expert list
Mode of inheritance for gene: NPRL3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NPRL3 were set to 27173016; 26285051
Phenotypes for gene: NPRL3 were set to Epilepsy, familial focal, with variable foci 3 (MIM#617118)
Review for gene: NPRL3 was set to GREEN
Added comment: Three families reported where focal cortical dysplasia is a feature, but also reduced penetrance noted. Borderline Amber/Green.
Sources: Expert list
Malformations of cortical development v2.13 NPRL2 Zornitza Stark gene: NPRL2 was added
gene: NPRL2 was added to Malformations of cortical development. Sources: Expert list
Mode of inheritance for gene: NPRL2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NPRL2 were set to 29281825; 27173016; 31625153
Phenotypes for gene: NPRL2 were set to Epilepsy, familial focal, with variable foci 2, MIM# 617116
Review for gene: NPRL2 was set to AMBER
Added comment: Focal cortical dysplasia reported in some patients

PMID: 29281825 (2017) - LOF variant identified in a patient with left frontal focal cortical dysplasia

PMID: 27173016 (2016) - cohort of focal epilepsy patients. LOF function variant in a family with focal epilepsy and focal cortical dysplasia. Segregated with two affected individuals but reduced penetrance and variable expressivity was observed.

Summary: associated with focal cortical dysplasia in two families. Recent review (PMID: 31625153) also states, mutations in NPRL2 have been linked to focal epilepsy with a less clear association with Focal Cortical Dysplasia.
Sources: Expert list
Malformations of cortical development v2.13 MAPK8IP3 Zornitza Stark gene: MAPK8IP3 was added
gene: MAPK8IP3 was added to Malformations of cortical development. Sources: Expert list
Mode of inheritance for gene: MAPK8IP3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MAPK8IP3 were set to 30612693
Phenotypes for gene: MAPK8IP3 were set to Neurodevelopmental disorder with or without variable brain abnormalities OMIM# 605431
Review for gene: MAPK8IP3 was set to GREEN
gene: MAPK8IP3 was marked as current diagnostic
Added comment: 13 unrelated individuals reported, with de novo truncating or missense variants (one recurrent). Brain anomalies such as perisylvian polymicrogyria, cerebral or cerebellar atrophy, and hypoplasia of the corpus callosum were consistent among individuals harboring recurrent de novo missense variants.
Sources: Expert list
Malformations of cortical development v2.13 MAP1B Zornitza Stark gene: MAP1B was added
gene: MAP1B was added to Malformations of cortical development. Sources: Expert list
Mode of inheritance for gene: MAP1B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MAP1B were set to 31317654; 30150678; 30214071
Phenotypes for gene: MAP1B were set to Periventricular nodular heterotopia 9, MIM# 618918
Review for gene: MAP1B was set to GREEN
gene: MAP1B was marked as current diagnostic
Added comment: At least 5 families described with intellectual disability and variable brain malformation phenotypes.
Sources: Expert list
Malformations of cortical development v2.13 LAMA2 Zornitza Stark gene: LAMA2 was added
gene: LAMA2 was added to Malformations of cortical development. Sources: Expert list
Mode of inheritance for gene: LAMA2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LAMA2 were set to 20207543; 18406646
Phenotypes for gene: LAMA2 were set to Muscular dystrophy, congenital, merosin deficient or partially deficient, MIM# 607855
Review for gene: LAMA2 was set to GREEN
gene: LAMA2 was marked as current diagnostic
Added comment: Malformations of cortical development are seen in a small proportion of individuals with biallelic LAMA2 variants. These were initially described and characterised based on immunohistochemistry showing loss of the protein associated with LAMA2. Reports where genotyping has been performed include: PMID: 20207543 – 7 individuals with biallelic LAMA2 variants and occipital agyria / polymicrogyria with a further 2 individuals with cortical folding abnormalities in other sites. PMID: 18406646 – 1 individual with a homozygous nonsense LAMA2 variant with extensive bilateral occipital polymicrogyria.
Sources: Expert list
Malformations of cortical development v2.13 GRIN2B Zornitza Stark gene: GRIN2B was added
gene: GRIN2B was added to Malformations of cortical development. Sources: Expert list
Mode of inheritance for gene: GRIN2B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GRIN2B were set to 28377535
Phenotypes for gene: GRIN2B were set to Mental retardation, autosomal dominant 6, MIM# 613970
Review for gene: GRIN2B was set to GREEN
Added comment: PMID: 28377535 - Neuroimaging was performed in 44 of 58 individuals: six unrelated individuals (6/44, 14%) showed a consistent MCD intermediate between typical polymicrogyria (PMG) and the cortical appearance of tubulinopathies, consisting of mixed large and small gyri separated by shallow sulci, a smooth grey-white border and little infolding. These individuals also had hypoplastic corpus callosum of varying degrees, enlarged and mildly dysplastic basal ganglia, hippocampal dysplasia with thick leaves and open hilus as well as enlarged tecta. One had no septum pellucidum. Generalised cerebral volume loss, compatible with cerebral atrophy, was described in four additional patients (4/44; 9%).
Sources: Expert list
Malformations of cortical development v2.13 GRIN1 Zornitza Stark gene: GRIN1 was added
gene: GRIN1 was added to Malformations of cortical development. Sources: Expert list
Mode of inheritance for gene: GRIN1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GRIN1 were set to 29365063
Phenotypes for gene: GRIN1 were set to Neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal dominant, MIM# 614254
Review for gene: GRIN1 was set to GREEN
gene: GRIN1 was marked as current diagnostic
Added comment: PMID: 29365063 - series of 11 unrelated individuals with GRIN1 variants and polymicrogyria
Sources: Expert list
Malformations of cortical development v2.13 FIG4 Zornitza Stark gene: FIG4 was added
gene: FIG4 was added to Malformations of cortical development. Sources: Expert list
Mode of inheritance for gene: FIG4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FIG4 were set to 18758830; 24598713
Phenotypes for gene: FIG4 were set to Polymicrogyria with epilepsy MIM# 612691
Review for gene: FIG4 was set to AMBER
Added comment: One family and a supportive mouse model:

PMID 18758830 – Ben Cheikh et al (2009) studied a large consanguineous Moroccan family in which bilateral occipital polymicrogyria segregated as an autosomal recessive trait, establishing linkage to 6q16-q22 by homozygosity mapping. Three affected individuals had epilepsy and polymicrogyria (other siblings had variable phenotypes).

PMID 24598713 – Baulac et al (2014) analysed the consanguineous Moroccan family and detected a homozygous missense variant in FIG4, which was homozygous in each of the affected siblings with polymicrogyria, heterozygous in one healthy sibling, not present in three healthy siblings, heterozygous in both parents and not tested in a further four siblings. They went on to study transfected fibroblasts from FIG4 deficient mice and examined histologically brains from FIG4-null mice which had findings that included changes “reminiscent of human cortical malformations”.
Sources: Expert list
Malformations of cortical development v2.13 FAT4 Zornitza Stark gene: FAT4 was added
gene: FAT4 was added to Malformations of cortical development. Sources: Expert list
Mode of inheritance for gene: FAT4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FAT4 were set to 22473091; 24056717
Phenotypes for gene: FAT4 were set to Van Maldergem syndrome 2, MIM# 615546
Review for gene: FAT4 was set to AMBER
Added comment: PVNH reported in two families.
Sources: Expert list
Malformations of cortical development v2.13 TUBGCP2 Arina Puzriakova Classified gene: TUBGCP2 as Amber List (moderate evidence)
Malformations of cortical development v2.13 TUBGCP2 Arina Puzriakova Added comment: Comment on list classification: There is enough evidence to rate this gene GREEN at the next major review - at least four families with three distinct TUBGCP2 variants, associated with a lissencephaly-spectrum phenotype.
Malformations of cortical development v2.13 TUBGCP2 Arina Puzriakova Gene: tubgcp2 has been classified as Amber List (Moderate Evidence).
Malformations of cortical development v2.12 TUBGCP2 Arina Puzriakova Tag for-review tag was added to gene: TUBGCP2.
Malformations of cortical development v2.12 TUBGCP2 Arina Puzriakova gene: TUBGCP2 was added
gene: TUBGCP2 was added to Malformations of cortical development. Sources: Literature
Mode of inheritance for gene: TUBGCP2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TUBGCP2 were set to 31630790
Phenotypes for gene: TUBGCP2 were set to Pachygyria, microcephaly, developmental delay, and dysmorphic facies, with or without seizures, 618737
Review for gene: TUBGCP2 was set to GREEN
Added comment: Associated with phenotype in OMIM, and a probable gene for Microcephaly and Lissencephaly Spectrum Disorders in G2P.

PMID: 31630790 (2019) - Five patients from four families with biallelic variants in the TUBGCP2 gene. Affected individuals shared phenotypic features that included progressive microcephaly (4/4), developmental delay (5/5, mild-severe), seizures (4/5). All patients exhibited lissencephaly-spectrum phenotypes with varying degrees of cortical malformations on brain imaging including pachygyria and subcortical band heterotopia.

All variants segregated with disease in each family. Analysis of fibroblasts derived from one patient with a splice site variant revealed several abnormal transcripts, predicted to result in LoF. No further functional studies of other variants or patient cells were performed.
Sources: Literature
Malformations of cortical development v2.11 EML1 Zornitza Stark gene: EML1 was added
gene: EML1 was added to Malformations of cortical development. Sources: Expert list
Mode of inheritance for gene: EML1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EML1 were set to 31710781
Phenotypes for gene: EML1 were set to Band heterotopia (MIM# 600348)
Review for gene: EML1 was set to GREEN
gene: EML1 was marked as current diagnostic
Added comment: PMID: 31710781; Review of 5 families with patients characterised by severe developmental delay, drug-resistant seizures and visual impairment. On brain imaging of 4 patients, there is megalencephaly with a characteristic ribbon-like subcortical heterotopia combined with partial or complete callosal agenesis and an overlying polymicrogyria-like cortical malformation.
Sources: Expert list
Malformations of cortical development v2.11 DEPDC5 Zornitza Stark gene: DEPDC5 was added
gene: DEPDC5 was added to Malformations of cortical development. Sources: Expert list
Mode of inheritance for gene: DEPDC5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DEPDC5 were set to 31444548
Phenotypes for gene: DEPDC5 were set to Epilepsy, familial focal, with variable foci 1 (MIM#604364)
Review for gene: DEPDC5 was set to GREEN
gene: DEPDC5 was marked as current diagnostic
Added comment: PMID: 31444548
- 5x focal cortical dysplasia patients
Sources: Expert list
Malformations of cortical development v2.11 DCHS1 Zornitza Stark gene: DCHS1 was added
gene: DCHS1 was added to Malformations of cortical development. Sources: Expert list
Mode of inheritance for gene: DCHS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DCHS1 were set to 27262615; 22473091
Phenotypes for gene: DCHS1 were set to Van Maldergem syndrome 1 (MIM#601390)
Review for gene: DCHS1 was set to GREEN
gene: DCHS1 was marked as current diagnostic
Added comment: PMID: 27262615;
- cohort of 26x periventricular band heterotopias and 2x had additional phenotype of pachygyria
- 2nd cohort of 10x band heterotopias

PMID: 22473091;
- 1x patient with localised areas of cortical thickening and gyral simplification
Sources: Literature
Sources: Expert list
Malformations of cortical development v2.11 DAG1 Zornitza Stark reviewed gene: DAG1: Rating: RED; Mode of pathogenicity: None; Publications: 24052401; Phenotypes: Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 9 (MIM#616538); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Malformations of cortical development v2.11 CTNNA2 Zornitza Stark gene: CTNNA2 was added
gene: CTNNA2 was added to Malformations of cortical development. Sources: Expert list
Mode of inheritance for gene: CTNNA2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CTNNA2 were set to 30013181
Phenotypes for gene: CTNNA2 were set to Cortical dysplasia, complex, with other brain malformations 9, MIM#618174
Review for gene: CTNNA2 was set to GREEN
gene: CTNNA2 was marked as current diagnostic
Added comment: 13 children from three unrelated families reported.
Sources: Expert list
Malformations of cortical development v2.11 CSNK2A1 Zornitza Stark reviewed gene: CSNK2A1: Rating: AMBER; Mode of pathogenicity: None; Publications: 27048600, 29240241; Phenotypes: Okur-Chung neurodevelopmental syndrome (MIM#617062); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Malformations of cortical development v2.11 PPP1R12A Arina Puzriakova Classified gene: PPP1R12A as Amber List (moderate evidence)
Malformations of cortical development v2.11 PPP1R12A Arina Puzriakova Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review - at least 5 unrelated cases reported with brain malformations associated with PPP1R12A variants.

PPP1R12A has been added to this panel following discussion with the clinical team.
Malformations of cortical development v2.11 PPP1R12A Arina Puzriakova Gene: ppp1r12a has been classified as Amber List (Moderate Evidence).
Malformations of cortical development v2.10 PPP1R12A Arina Puzriakova gene: PPP1R12A was added
gene: PPP1R12A was added to Malformations of cortical development. Sources: Literature
for-review tags were added to gene: PPP1R12A.
Mode of inheritance for gene: PPP1R12A was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PPP1R12A were set to 31883643
Phenotypes for gene: PPP1R12A were set to Genitourinary and/or/brain malformation syndrome, 618820
Review for gene: PPP1R12A was set to GREEN
Added comment: Associated with phenotype in OMIM, and a probable gene for PPP1R12A-related Holoprosencephaly Spectrum and Urogenital Malformations in G2P.

PMID: 31883643 (2020) - Screening cohorts of patients with holoprosencephaly and patients with disorders of sex development revealed 12 unrelated individuals with de novo LoF variants in the PPP1R12A gene. Variants were associated with a broad spectrum of manifestations, and a clear genotype-phenotype correlation was not observed - most commonly presentation included either malformations of the brain or the genitourinary tract (two individuals exhibited both brain and genitourinary anomalies). 5/12 individuals presented structural CNS anomalies; however, the phenotype was variable and included dysgenesis of the corpus callosum, polymicrogyria, leukomalacia, and acrania.
Sources: Literature
Malformations of cortical development v2.9 MN1 Arina Puzriakova changed review comment from: Over 20 unrelated probands reported with heterozygous MN1 truncating variants, associated with a distinct phenotype which includes DD, craniofacial abnormalities, hearing loss, and structural abnormalities in the brain (e.g. polymicrogyria, dysmorphic corpus callosum and anomalies of the cerebellum).

Most variants cluster in the C-terminal, and all were predicted to escape NMD. Authors postulated that the resulting truncated protein may have a dominant-negative or gain-of-function effect. Also phenotypically supportive knockout mouse model.
Sources: Literature; to: Associated with phenotype in OMIM, and a probable gene for MN1 C-terminal truncation syndrome in G2P.

Over 20 unrelated probands reported with heterozygous MN1 truncating variants, associated with a distinct phenotype which includes DD, craniofacial abnormalities, hearing loss, and structural abnormalities in the brain (e.g. polymicrogyria, dysmorphic corpus callosum and anomalies of the cerebellum).

Most variants cluster in the C-terminal, and all were predicted to escape NMD. Authors postulated that the resulting truncated protein may have a dominant-negative or gain-of-function effect. Also phenotypically supportive knockout mouse model.
Sources: Literature
Malformations of cortical development v2.9 MN1 Arina Puzriakova Classified gene: MN1 as Amber List (moderate evidence)
Malformations of cortical development v2.9 MN1 Arina Puzriakova Added comment: Comment on list classification: There is enough evidence to rate this gene GREEN at the next major review - added to this panel following suggestion from the clinical team.
Malformations of cortical development v2.9 MN1 Arina Puzriakova Gene: mn1 has been classified as Amber List (Moderate Evidence).
Malformations of cortical development v2.8 MN1 Arina Puzriakova gene: MN1 was added
gene: MN1 was added to Malformations of cortical development. Sources: Literature
for-review tags were added to gene: MN1.
Mode of inheritance for gene: MN1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: MN1 were set to 31834374; 31839203; 15870292
Phenotypes for gene: MN1 were set to CEBALID syndrome, 618774
Review for gene: MN1 was set to GREEN
Added comment: Over 20 unrelated probands reported with heterozygous MN1 truncating variants, associated with a distinct phenotype which includes DD, craniofacial abnormalities, hearing loss, and structural abnormalities in the brain (e.g. polymicrogyria, dysmorphic corpus callosum and anomalies of the cerebellum).

Most variants cluster in the C-terminal, and all were predicted to escape NMD. Authors postulated that the resulting truncated protein may have a dominant-negative or gain-of-function effect. Also phenotypically supportive knockout mouse model.
Sources: Literature
Malformations of cortical development v2.7 B4GAT1 Zornitza Stark reviewed gene: B4GAT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 23359570, 23877401, 23359570, 23217742; Phenotypes: Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 13 MIM# 615287; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Malformations of cortical development v2.7 ATP1A2 Zornitza Stark gene: ATP1A2 was added
gene: ATP1A2 was added to Malformations of cortical development. Sources: Expert list
Mode of inheritance for gene: ATP1A2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATP1A2 were set to 31608932
Phenotypes for gene: ATP1A2 were set to hydrops fetalis; microcephaly; arthrogryposis; extensive cortical malformations
Review for gene: ATP1A2 was set to GREEN
gene: ATP1A2 was marked as current diagnostic
Added comment: Three individuals from two unrelated families reported with balleliic LoF variants in this gene and hydrops/congenital abnormalities including extensive cortical malformations. Mouse model is perinatal lethal. This is a distinct phenotype from the mono allelic variants associated with alternating hemiplegia.
Sources: Expert list
Malformations of cortical development v2.7 ARF1 Zornitza Stark gene: ARF1 was added
gene: ARF1 was added to Malformations of cortical development. Sources: Expert list
Mode of inheritance for gene: ARF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ARF1 were set to 28868155
Phenotypes for gene: ARF1 were set to Periventricular nodular heterotopia 8, MIM# 618185
Review for gene: ARF1 was set to GREEN
gene: ARF1 was marked as current diagnostic
Added comment: Three unrelated individuals reported with de novo missense in this gene.
Sources: Expert list
Malformations of cortical development v2.7 APC2 Zornitza Stark gene: APC2 was added
gene: APC2 was added to Malformations of cortical development. Sources: Expert list
Mode of inheritance for gene: APC2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: APC2 were set to 31585108
Phenotypes for gene: APC2 were set to Cortical dysplasia, complex, with other brain malformations 10, MIM#618677
Review for gene: APC2 was set to GREEN
gene: APC2 was marked as current diagnostic
Added comment: 12 individuals from 8 unrelated families; intellectual disability, seizures, cortical dysplasia including posterior to anterior predominant pattern of lissencephaly, heterotopias, paucity of white matter, thin corpus callosum.
Sources: Expert list
Malformations of cortical development v2.7 CRADD Zornitza Stark gene: CRADD was added
gene: CRADD was added to Malformations of cortical development. Sources: Expert list
Mode of inheritance for gene: CRADD was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CRADD were set to 27773430
Phenotypes for gene: CRADD were set to Mental retardation, autosomal recessive 34, with variant lissencephaly, MIM# 614499
Review for gene: CRADD was set to GREEN
gene: CRADD was marked as current diagnostic
Added comment: At least 5 families reported though some were from the Pennsylvania Mennonite population, and had same founder variant (but at least 4 unique variants reported). Brain imaging shows a mild variant of lissencephaly with anterior-predominant pachygyria with shallow and unusually wide sulci and mildly thickened cortex.
Sources: Expert list
Malformations of cortical development v2.7 CDK13 Zornitza Stark reviewed gene: CDK13: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Congenital heart defects, dysmorphic facial features, and intellectual developmental disorder, MIM# 617360; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Malformations of cortical development v2.7 PEX7 Zornitza Stark reviewed gene: PEX7: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Peroxisome biogenesis disorder 9B (MIM#614879), Rhizomelic chondrodysplasia punctata, type 1 (MIM#215100); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Malformations of cortical development v2.7 VLDLR Zornitza Stark gene: VLDLR was added
gene: VLDLR was added to Malformations of cortical development. Sources: Expert list
Mode of inheritance for gene: VLDLR was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: VLDLR were set to 16080122; 18364738; 18326629; 22700954; 22973972
Phenotypes for gene: VLDLR were set to Cerebellar hypoplasia and mental retardation with or without quadrupedal locomotion 1 (MIM#224050)
Review for gene: VLDLR was set to GREEN
gene: VLDLR was marked as current diagnostic
Added comment: Gyral simplification/pachygyria reported in this condition.
Sources: Expert list
Malformations of cortical development v2.7 MCF2 Zornitza Stark gene: MCF2 was added
gene: MCF2 was added to Malformations of cortical development. Sources: Literature
Mode of inheritance for gene: MCF2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: MCF2 were set to 31846234
Phenotypes for gene: MCF2 were set to Perisylvian polymicrogyria
Review for gene: MCF2 was set to RED
Added comment: Single individual reported, inherited missense variant from unaffected mother, some support from mouse model.
Sources: Literature
Malformations of cortical development v2.7 TUBB2A Arina Puzriakova edited their review of gene: TUBB2A: Changed publications: 32571897
Malformations of cortical development v2.7 TUBB2A Arina Puzriakova reviewed gene: TUBB2A: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Cortical dysplasia, complex, with other brain malformations 5, 615763; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Malformations of cortical development v2.7 TMX2 Sarah Leigh Classified gene: TMX2 as Green List (high evidence)
Malformations of cortical development v2.7 TMX2 Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM and as probable Gen2Phen gene for Primary microcephaly, cortical malformation and epileptic encephalopathy. At least 7 variants reported in at least 9 unrelated cases of Neurodevelopmental disorder with microcephaly, cortical malformations, and spasticity 618730 (PMID 31735293; 31270415).
Malformations of cortical development v2.7 TMX2 Sarah Leigh Gene: tmx2 has been classified as Green List (High Evidence).
Malformations of cortical development v2.6 TMX2 Sarah Leigh gene: TMX2 was added
gene: TMX2 was added to Malformations of cortical development. Sources: Literature
Mode of inheritance for gene: TMX2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TMX2 were set to 31586943; 31735293; 31270415
Phenotypes for gene: TMX2 were set to Neurodevelopmental disorder with microcephaly, cortical malformations, and spasticity 618730
Review for gene: TMX2 was set to GREEN
Added comment: Sources: Literature
Malformations of cortical development v2.5 EMX2 Zornitza Stark changed review comment from: Please note publication disputing gene-disease association.; to: Please note publication disputing gene-disease association. Also note only pathogenic variants in ClinVar are from 1996, all the rest are VOUS/LB.
Malformations of cortical development v2.5 EMX2 Zornitza Stark reviewed gene: EMX2: Rating: AMBER; Mode of pathogenicity: None; Publications: 18409201; Phenotypes: Schizencephaly, 269160; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Malformations of cortical development v2.4 CEP85L Zornitza Stark gene: CEP85L was added
gene: CEP85L was added to Malformations of cortical development. Sources: Literature
Mode of inheritance for gene: CEP85L was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CEP85L were set to 32097630
Phenotypes for gene: CEP85L were set to Lissencephaly, posterior predominant
Review for gene: CEP85L was set to GREEN
Added comment: Thirteen individuals reported with mono allelic variants in this gene, inherited in two of the families. Mouse model had neuronal migration defects.
Sources: Literature
Malformations of cortical development v2.4 Catherine Snow Panel version has been signed off
Malformations of cortical development v2.3 Catherine Snow Panel types changed to Rare Disease 100K; GMS Rare Disease; Component Of Super Panel; GMS signed-off
Malformations of cortical development v2.1 Louise Daugherty Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual; GMS Rare Disease; Component Of Super Panel; GMS signed-off
Malformations of cortical development v2.0 Louise Daugherty promoted panel to version 2.0
Malformations of cortical development v1.172 Louise Daugherty Panel types changed to Rare Disease 100K; GMS Rare Disease; Component Of Super Panel; GMS signed-off
Malformations of cortical development v1.171 KIF1BP Louise Daugherty Tag new-gene-name tag was added to gene: KIF1BP.
Malformations of cortical development v1.171 KIF1BP Louise Daugherty commented on gene: KIF1BP
Malformations of cortical development v1.171 EMX2 Louise Daugherty Classified gene: EMX2 as Green List (high evidence)
Malformations of cortical development v1.171 EMX2 Louise Daugherty Gene: emx2 has been classified as Green List (High Evidence).
Malformations of cortical development v1.170 EMX2 Louise Daugherty changed review comment from: From review Rebecca Foulger (Genomics England curator) [email protected]
Review from Genetic epilepsy syndromes panel:
Comment on list classification: Updated rating from Amber to Green: Green review by Zornitza and 3 cases of Schizencephaly patients with EMX2 variants and partial epilepsy in PMID:9359037. PMID:15921232 (2005) report that half of Schizencephaly patients show epilepsy. Therefore sufficient evidence for inclusion on panel.
Created: 29 Nov 2018, 11:05 a.m.

Faiella et al., 1997 (PMID:9359037) summarise 10 patients with Schizencephaly. 6 patients were heterozygous for de novo variants in EMX2 (including 2 brothers). 3 of these unrelated patients have partial epilepsy (patients VF, MB and PB).
Created: 29 Nov 2018, 11:03 a.m. | Last Modified: 22 Jul 2019, 12:16 p.m.

Panel Version: 1.173; to: From review Rebecca Foulger (Genomics England curator) Review from Genetic epilepsy syndromes panel:
Comment on list classification: Updated rating from Amber to Green: Green review by Zornitza and 3 cases of Schizencephaly patients with EMX2 variants and partial epilepsy in PMID:9359037. PMID:15921232 (2005) report that half of Schizencephaly patients show epilepsy. Therefore sufficient evidence for inclusion on panel.
Created: 29 Nov 2018, 11:05 a.m.

Faiella et al., 1997 (PMID:9359037) summarise 10 patients with Schizencephaly. 6 patients were heterozygous for de novo variants in EMX2 (including 2 brothers). 3 of these unrelated patients have partial epilepsy (patients VF, MB and PB).
Created: 29 Nov 2018, 11:03 a.m. | Last Modified: 22 Jul 2019, 12:16 p.m.

Panel Version: 1.173
Malformations of cortical development v1.170 EMX2 Louise Daugherty changed review comment from: From review
Rebecca Foulger (Genomics England curator)
[email protected]
I don't know

Review from Genetic epilepsy syndromes panel:

Comment on list classification: Updated rating from Amber to Green: Green review by Zornitza and 3 cases of Schizencephaly patients with EMX2 variants and partial epilepsy in PMID:9359037. PMID:15921232 (2005) report that half of Schizencephaly patients show epilepsy. Therefore sufficient evidence for inclusion on panel.
Created: 29 Nov 2018, 11:05 a.m.

Faiella et al., 1997 (PMID:9359037) summarise 10 patients with Schizencephaly. 6 patients were heterozygous for de novo variants in EMX2 (including 2 brothers). 3 of these unrelated patients have partial epilepsy (patients VF, MB and PB).
Created: 29 Nov 2018, 11:03 a.m. | Last Modified: 22 Jul 2019, 12:16 p.m.

Panel Version: 1.173; to: From review Rebecca Foulger (Genomics England curator) [email protected]
Review from Genetic epilepsy syndromes panel:
Comment on list classification: Updated rating from Amber to Green: Green review by Zornitza and 3 cases of Schizencephaly patients with EMX2 variants and partial epilepsy in PMID:9359037. PMID:15921232 (2005) report that half of Schizencephaly patients show epilepsy. Therefore sufficient evidence for inclusion on panel.
Created: 29 Nov 2018, 11:05 a.m.

Faiella et al., 1997 (PMID:9359037) summarise 10 patients with Schizencephaly. 6 patients were heterozygous for de novo variants in EMX2 (including 2 brothers). 3 of these unrelated patients have partial epilepsy (patients VF, MB and PB).
Created: 29 Nov 2018, 11:03 a.m. | Last Modified: 22 Jul 2019, 12:16 p.m.

Panel Version: 1.173
Malformations of cortical development v1.170 EMX2 Louise Daugherty commented on gene: EMX2: From review
Rebecca Foulger (Genomics England curator)
[email protected]
I don't know

Review from Genetic epilepsy syndromes panel:

Comment on list classification: Updated rating from Amber to Green: Green review by Zornitza and 3 cases of Schizencephaly patients with EMX2 variants and partial epilepsy in PMID:9359037. PMID:15921232 (2005) report that half of Schizencephaly patients show epilepsy. Therefore sufficient evidence for inclusion on panel.
Created: 29 Nov 2018, 11:05 a.m.

Faiella et al., 1997 (PMID:9359037) summarise 10 patients with Schizencephaly. 6 patients were heterozygous for de novo variants in EMX2 (including 2 brothers). 3 of these unrelated patients have partial epilepsy (patients VF, MB and PB).
Created: 29 Nov 2018, 11:03 a.m. | Last Modified: 22 Jul 2019, 12:16 p.m.

Panel Version: 1.173
Malformations of cortical development v1.170 EMX2 Louise Daugherty gene: EMX2 was added
gene: EMX2 was added to Malformations of cortical development. Sources: Other
Mode of inheritance for gene: EMX2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: EMX2 were set to 8528262; 9359037
Phenotypes for gene: EMX2 were set to Schizencephaly, 269160
Review for gene: EMX2 was set to GREEN
Added comment: Due to a webex to discuss R59 (https://panelapp.genomicsengland.co.uk/panels/489/) on Aug 8th 2019 (RF, EM, RS with WWMGLH), some discussion points overlapped with additional panels and it was agreed that EMX2 should be added to the : Malformations of cortical development panel : https://panelapp.genomicsengland.co.uk/panels/96/ which a component of the GMS Super panels: https://panelapp.genomicsengland.co.uk/panels/96/ and Cerebral malformations (https://panelapp.genomicsengland.co.uk/panels/491/).
Phenotype is: Schizencephaly
Sources: Other
Malformations of cortical development v1.167 MACF1 Rebecca Foulger Added comment: Comment on mode of pathogenicity: Updated Mode of pathogenicity to match the 'Intellectual disability' and 'Genetic epilepsy syndromes' panels.
Malformations of cortical development v1.167 MACF1 Rebecca Foulger Mode of pathogenicity for gene: MACF1 was changed from None to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Malformations of cortical development v1.166 MACF1 Rebecca Foulger Classified gene: MACF1 as Green List (high evidence)
Malformations of cortical development v1.166 MACF1 Rebecca Foulger Added comment: Comment on list classification: Green rating agreed by Helen Brittain based on multiple unrelated cases in PMID:30471716.
Malformations of cortical development v1.166 MACF1 Rebecca Foulger Gene: macf1 has been classified as Green List (High Evidence).
Malformations of cortical development v1.165 MACF1 Rebecca Foulger gene: MACF1 was added
gene: MACF1 was added to Malformations of cortical development. Sources: Literature
Mode of inheritance for gene: MACF1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: MACF1 were set to 30471716
Phenotypes for gene: MACF1 were set to Lissencephaly 9 with complex brainstem malformation, 618325
Review for gene: MACF1 was set to GREEN
Added comment: Added MACF1 to 'Malformations of cortical development' panel on advice from Helen Brittain after MACF1 was reviewed by Sarah Leigh on the 'Genetic Epilepsy Syndromes' and 'Intellectual disability' panels. PMID:30471716 (Dobyns et al 2018) recognized a complex brainstem malformation in three unrelated children with MACF1 variants. They searched their large brain-malformation databases and found another five children with this malformation (as well as one with a less severe variant). The brain malformation comprised posterior predominant lissencephaly and midline crossing defects consisting of absent anterior commissure and a striking W-shaped brainstem malformation caused by small or absent pontine crossing fibers.
Sources: Literature
Malformations of cortical development v1.164 ISPD Louise Daugherty commented on gene: ISPD
Malformations of cortical development v1.164 ISPD Louise Daugherty Tag new-gene-name tag was added to gene: ISPD.
Malformations of cortical development v1.164 Louise Daugherty Panel types changed to Rare Disease 100K; GMS Rare Disease; Component Of Super Panel
Malformations of cortical development v1.163 Ellen McDonagh Panel types changed to Rare Disease 100K; GMS Rare Disease
Malformations of cortical development v1.161 Ellen McDonagh List of related panels changed from to
Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual
Malformations of cortical development v1.160 TUBA8 Rebecca Foulger Tag watchlist tag was added to gene: TUBA8.
Malformations of cortical development v1.160 TUBA8 Rebecca Foulger Classified gene: TUBA8 as Amber List (moderate evidence)
Malformations of cortical development v1.160 TUBA8 Rebecca Foulger Added comment: Comment on list classification: Demoted from Green to Amber based on re-review of evidence. Demotion was agreed by Clinical Fellow Helen Brittain.

TUBA8 was originally rated Green on the panel because TUBA8 is a confirmed DD-G2P gene for 'POLYMICROGYRIA WITH OPTIC NERVE HYPOPLASIA' (the former name for Cortical dysplasia, complex, with other brain malformations 8, 613180) and TUBA8 is on the UKGTN 43 gene panel for brain malformations:
https://ukgtn.nhs.uk/find-a-test/search-by-disorder-gene/brain-malformation-disorders-cortical-43-gene-panel-886/.

However, the reported evidence comes from one 2009 paper (PMID:19896110) with 4 literature cases coming from 2 consaguineous families (1 variant); at least PMID:25008804 questions whether the families are related. A 2017 paper identifies an additional VUS (compound heterozygous) in a chinese EE patient (PMID:29588952).

Anna de Burca confirmed that there are lots of cases with CNVs involving TUBA8 in DECIPHER but there are only two cases with SNVs in the gene. One of them is classified as unknown pathogenicity, the other likely benign.

I contacted Usha Kini at Oxford, and also the Leeds and Cardiff genetic testing groups (as recommended by Usha) since they all offer cortical malformation panels. All three confirmed (pers. comm. via email) that they have no further cases for TUBA8.

The literature evidence and communications from Oxford, Leeds and Cardiff all support demotion of TUBA8 to Amber rating: The phenotype is still appropriate for the panel but insufficient cases for diagnostic rating.

Added 'watchlist' tag to look out for further cases.
Malformations of cortical development v1.160 TUBA8 Rebecca Foulger Gene: tuba8 has been classified as Amber List (Moderate Evidence).
Malformations of cortical development v1.159 TUBA8 Rebecca Foulger Added comment: Comment on mode of inheritance: Biallelic MOI supported by OMIM and DD-Gene2Phenotype.
Malformations of cortical development v1.159 TUBA8 Rebecca Foulger Mode of inheritance for gene: TUBA8 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Malformations of cortical development v1.158 SMO Rebecca Foulger Added comment: Comment on mode of inheritance: Changed MOI from 'Other' in order to capture variants within this gene in our current tiering pipeline.
Malformations of cortical development v1.158 SMO Rebecca Foulger Mode of inheritance for gene: SMO was changed from Other - please specifiy in evaluation comments to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Malformations of cortical development v1.157 MTOR Rebecca Foulger Classified gene: MTOR as Green List (high evidence)
Malformations of cortical development v1.157 MTOR Rebecca Foulger Added comment: Comment on list classification: Promoted from Amber to Green due to ID panel review there is enough evidence to support MTOR and Focal cortical dysplasia, type II.
Malformations of cortical development v1.157 MTOR Rebecca Foulger Gene: mtor has been classified as Green List (High Evidence).
Malformations of cortical development v1.156 TUBB Rebecca Foulger Classified gene: TUBB as Green List (high evidence)
Malformations of cortical development v1.156 TUBB Rebecca Foulger Added comment: Comment on list classification: Updated rating from Amber to Green following reassessment of evidence as suggested by Helen Brittain, TUBB is a confirmed Gene2Phenotype gene for cortical dysplasia disorder (MIM:615771). Plus 3 unrelated cases from the literature (PMID:23246003).
Malformations of cortical development v1.156 TUBB Rebecca Foulger Gene: tubb has been classified as Green List (High Evidence).
Malformations of cortical development v1.155 TUBB Rebecca Foulger commented on gene: TUBB: In 3 unrelated children of different ethnicities with complex cortical dysplasia with other brain malformations-6 (MIM:615771) and microcephaly, Breuss et al. (2012, PMID:23246003) identified 3 different de novo heterozygous missense variants in the TUBB gene.
Malformations of cortical development v1.155 TUBB Rebecca Foulger Publications for gene: TUBB were set to 27010057, 23246003; 30016746
Malformations of cortical development v1.154 TUBB Rebecca Foulger Added comment: Comment on publications: TUBB is called TUBB5 in some literature (e.g. PMID:23246003).
Malformations of cortical development v1.154 TUBB Rebecca Foulger Publications for gene: TUBB were set to 27010057, 23246003
Malformations of cortical development v1.153 TUBB Rebecca Foulger Phenotypes for gene: TUBB were changed from Cortical dysplasia, complex, with other brain malformations 6 to Cortical dysplasia, complex, with other brain malformations 6, 615771
Malformations of cortical development v1.152 ISCA-37430-Loss Louise Daugherty Region: ISCA-37430-Loss was added
Region: ISCA-37430-Loss was added to Malformations of cortical development. Sources: ClinGen,Expert Review Green
Mode of inheritance for Region: ISCA-37430-Loss was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for Region: ISCA-37430-Loss were set to microcephaly, dysgenesis of the corpus callosum, and cerebellar atrophy, as well as neurobehavioral disorders, including delayed development, mental retardation, and attention deficit-hyperactivity disorder. Patients with duplications of YWHAE tended to have macrosomia, facial dysmorphism, and mild developmental delay; growth restriction, craniofacial dysmorphisms, structural abnormalities of brain and cognitive impairment; Chromosome 17p13.3 duplication syndrome; prominent forehead, bitemporal hollowing, short nose with upturned nares, protuberant upper lip, thin vermilion border, and small jaw; Characteristic facies, pre- and post-natal growth retardation; 247200; classic lissencephaly (pachygyria, incomplete or absent gyration of the cerebrum), microcephaly, wrinkled skin over the glabella and frontal suture, prominent occiput, narrow forehead, downward slanting palpebral fissures, small nose and chin, cardiac malformations, hypoplastic male extrenal genitalia, growth retardation, and mental deficiency with seizures and EEG abnormalities; Miller-Dieker lissencephaly syndrome
Malformations of cortical development OSGEP Helen Brittain marked gene: OSGEP as ready
Malformations of cortical development OSGEP Helen Brittain classified OSGEP as Green List (high evidence)
Malformations of cortical development OSGEP Helen Brittain Added gene to panel
Malformations of cortical development PEX11A Louise Daugherty edited their review of PEX11A
Malformations of cortical development PEX11A Louise Daugherty Added gene to panel
Malformations of cortical development PEX7 Helen Brittain reviewed PEX7
Malformations of cortical development PEX6 Helen Brittain reviewed PEX6
Malformations of cortical development PEX5 Helen Brittain reviewed PEX5
Malformations of cortical development PEX3 Helen Brittain reviewed PEX3
Malformations of cortical development PEX26 Helen Brittain reviewed PEX26
Malformations of cortical development PEX2 Helen Brittain reviewed PEX2
Malformations of cortical development PEX19 Helen Brittain reviewed PEX19
Malformations of cortical development PEX16 Helen Brittain reviewed PEX16
Malformations of cortical development PEX14 Helen Brittain reviewed PEX14
Malformations of cortical development PEX13 Helen Brittain reviewed PEX13
Malformations of cortical development PEX12 Helen Brittain reviewed PEX12
Malformations of cortical development PEX11B Helen Brittain reviewed PEX11B
Malformations of cortical development PEX10 Helen Brittain reviewed PEX10
Malformations of cortical development PEX1 Helen Brittain reviewed PEX1
Malformations of cortical development PEX7 Louise Daugherty Added gene to panel
Malformations of cortical development PEX6 Louise Daugherty Added gene to panel
Malformations of cortical development PEX5 Louise Daugherty Added gene to panel
Malformations of cortical development PEX3 Louise Daugherty Added gene to panel
Malformations of cortical development PEX26 Louise Daugherty Added gene to panel
Malformations of cortical development PEX2 Louise Daugherty Added gene to panel
Malformations of cortical development PEX19 Louise Daugherty Added gene to panel
Malformations of cortical development PEX16 Louise Daugherty Added gene to panel
Malformations of cortical development PEX14 Louise Daugherty Added gene to panel
Malformations of cortical development PEX13 Louise Daugherty Added gene to panel
Malformations of cortical development PEX12 Louise Daugherty Added gene to panel
Malformations of cortical development PEX11B Louise Daugherty Added gene to panel
Malformations of cortical development PEX10 Louise Daugherty Added gene to panel
Malformations of cortical development PEX1 Louise Daugherty Added gene to panel
Malformations of cortical development TMEM5 Louise Daugherty commented on TMEM5
Malformations of cortical development EOMES Ellen McDonagh commented on EOMES
Malformations of cortical development EOMES Ellen McDonagh Added gene to panel
Malformations of cortical development CDK13 Ellen McDonagh classified CDK13 as Green List (high evidence)
Malformations of cortical development TSC2 Ellen McDonagh classified TSC2 as red
Malformations of cortical development TSC2 Ellen McDonagh added TSC2 to panel
Malformations of cortical development TSC2 Ellen McDonagh reviewed TSC2
Malformations of cortical development TSC1 Ellen McDonagh classified TSC1 as amber
Malformations of cortical development TSC1 Ellen McDonagh added TSC1 to panel
Malformations of cortical development TSC1 Ellen McDonagh reviewed TSC1
Malformations of cortical development MTOR Ellen McDonagh classified MTOR as amber
Malformations of cortical development MTOR Ellen McDonagh added MTOR to panel
Malformations of cortical development MTOR Ellen McDonagh reviewed MTOR
Malformations of cortical development SMO Louise Daugherty classified SMO as green
Malformations of cortical development SMO Louise Daugherty commented on SMO
Malformations of cortical development SMO Louise Daugherty commented on SMO
Malformations of cortical development SMO Louise Daugherty added SMO to panel
Malformations of cortical development SMO Louise Daugherty reviewed SMO
Malformations of cortical development AKT3 Ellen McDonagh commented on AKT3
Malformations of cortical development FLNA Ellen McDonagh commented on FLNA
Malformations of cortical development CSNK2A1 Richard Scott marked CSNK2A1 as ready
Malformations of cortical development CSNK2A1 Richard Scott classified CSNK2A1 as green
Malformations of cortical development CSNK2A1 Richard Scott added CSNK2A1 to panel
Malformations of cortical development CSNK2A1 Richard Scott reviewed CSNK2A1
Malformations of cortical development Ellen McDonagh approved panel
Malformations of cortical development TUBB3 Alice Gardham classified TUBB3 as green
Malformations of cortical development TUBB3 Alice Gardham commented on TUBB3
Malformations of cortical development TUBB3 Alice Gardham classified TUBB3 as green
Malformations of cortical development B3GALNT2 Alice Gardham marked B3GALNT2 as ready
Malformations of cortical development B3GALNT2 Alice Gardham classified B3GALNT2 as green
Malformations of cortical development B3GALNT2 Alice Gardham added B3GALNT2 to panel
Malformations of cortical development B3GALNT2 Alice Gardham reviewed B3GALNT2
Malformations of cortical development GMPPB Alice Gardham marked GMPPB as ready
Malformations of cortical development GMPPB Alice Gardham added GMPPB to panel
Malformations of cortical development GMPPB Alice Gardham reviewed GMPPB
Malformations of cortical development TMEM5 Alice Gardham marked TMEM5 as ready
Malformations of cortical development TMEM5 Alice Gardham added TMEM5 to panel
Malformations of cortical development TMEM5 Alice Gardham reviewed TMEM5
Malformations of cortical development B4GAT1 Alice Gardham marked B4GAT1 as ready
Malformations of cortical development B4GAT1 Alice Gardham added B4GAT1 to panel
Malformations of cortical development B4GAT1 Alice Gardham reviewed B4GAT1
Malformations of cortical development DAG1 Alice Gardham marked DAG1 as ready
Malformations of cortical development DAG1 Alice Gardham added DAG1 to panel
Malformations of cortical development DAG1 Alice Gardham reviewed DAG1
Malformations of cortical development POMGNT2 Alice Gardham marked POMGNT2 as ready
Malformations of cortical development POMGNT2 Alice Gardham added POMGNT2 to panel
Malformations of cortical development POMGNT2 Alice Gardham reviewed POMGNT2
Malformations of cortical development POMK Alice Gardham marked POMK as ready
Malformations of cortical development POMK Alice Gardham added POMK to panel
Malformations of cortical development POMK Alice Gardham reviewed POMK
Malformations of cortical development ASPM Alice Gardham marked ASPM as ready
Malformations of cortical development ASPM Alice Gardham added ASPM to panel
Malformations of cortical development ASPM Alice Gardham reviewed ASPM
Malformations of cortical development KIAA1279 Alice Gardham marked KIAA1279 as ready
Malformations of cortical development KIAA1279 Alice Gardham added KIAA1279 to panel
Malformations of cortical development KIAA1279 Alice Gardham reviewed KIAA1279
Malformations of cortical development GPSM2 Alice Gardham marked GPSM2 as ready
Malformations of cortical development GPSM2 Alice Gardham classified GPSM2 as green
Malformations of cortical development GPSM2 Alice Gardham added GPSM2 to panel
Malformations of cortical development GPSM2 Alice Gardham reviewed GPSM2
Malformations of cortical development TUBA1A Alice Gardham marked TUBA1A as ready
Malformations of cortical development PAFAH1B1 Alice Gardham marked PAFAH1B1 as ready
Malformations of cortical development NDE1 Alice Gardham marked NDE1 as ready
Malformations of cortical development KATNB1 Alice Gardham marked KATNB1 as ready
Malformations of cortical development FLNA Alice Gardham marked FLNA as ready
Malformations of cortical development DCX Alice Gardham marked DCX as ready
Malformations of cortical development ARX Alice Gardham marked ARX as ready
Malformations of cortical development ADGRG1 Alice Gardham marked ADGRG1 as ready
Malformations of cortical development RTTN Alice Gardham marked RTTN as ready
Malformations of cortical development RTTN Alice Gardham added RTTN to panel
Malformations of cortical development RTTN Alice Gardham reviewed RTTN
Malformations of cortical development OCLN Alice Gardham marked OCLN as ready
Malformations of cortical development OCLN Alice Gardham classified OCLN as green
Malformations of cortical development OCLN Alice Gardham added OCLN to panel
Malformations of cortical development OCLN Alice Gardham reviewed OCLN
Malformations of cortical development ISPD Alice Gardham marked ISPD as ready
Malformations of cortical development ISPD Alice Gardham added ISPD to panel
Malformations of cortical development ISPD Alice Gardham reviewed ISPD
Malformations of cortical development FKTN Alice Gardham marked FKTN as ready
Malformations of cortical development FKTN Alice Gardham added FKTN to panel
Malformations of cortical development FKTN Alice Gardham reviewed FKTN
Malformations of cortical development ERMARD Alice Gardham marked ERMARD as ready
Malformations of cortical development ERMARD Alice Gardham added ERMARD to panel
Malformations of cortical development ERMARD Alice Gardham reviewed ERMARD
Malformations of cortical development CCND2 Alice Gardham marked CCND2 as ready
Malformations of cortical development CCND2 Alice Gardham classified CCND2 as green
Malformations of cortical development CCND2 Alice Gardham added CCND2 to panel
Malformations of cortical development CCND2 Alice Gardham reviewed CCND2
Malformations of cortical development TUBG1 Alice Gardham marked TUBG1 as ready
Malformations of cortical development TUBG1 Alice Gardham classified TUBG1 as green
Malformations of cortical development TUBG1 Alice Gardham reviewed TUBG1
Malformations of cortical development TUBB Alice Gardham marked TUBB as ready
Malformations of cortical development TUBB Alice Gardham classified TUBB as amber
Malformations of cortical development TUBB2A Alice Gardham marked TUBB2A as ready
Malformations of cortical development TUBB2A Alice Gardham classified TUBB2A as green
Malformations of cortical development TUBB2A Alice Gardham reviewed TUBB2A
Malformations of cortical development RELN Alice Gardham marked RELN as ready
Malformations of cortical development RELN Alice Gardham classified RELN as green
Malformations of cortical development LAMC3 Alice Gardham marked LAMC3 as ready
Malformations of cortical development LAMC3 Alice Gardham commented on LAMC3
Malformations of cortical development KIF5C Alice Gardham marked KIF5C as ready
Malformations of cortical development KIF5C Alice Gardham commented on KIF5C
Malformations of cortical development KIF5C Alice Gardham classified KIF5C as green
Malformations of cortical development KIF2A Alice Gardham marked KIF2A as ready
Malformations of cortical development KIF2A Alice Gardham commented on KIF2A
Malformations of cortical development KIF2A Alice Gardham classified KIF2A as green
Malformations of cortical development TUBA8 Alice Gardham marked TUBA8 as ready
Malformations of cortical development TUBA8 Alice Gardham commented on TUBA8
Malformations of cortical development TUBB2B Alice Gardham marked TUBB2B as ready
Malformations of cortical development TUBB2B Alice Gardham reviewed TUBB2B
Malformations of cortical development TUBB3 Alice Gardham marked TUBB3 as ready
Malformations of cortical development TUBB Alice Gardham reviewed TUBB
Malformations of cortical development PIK3R2 Alice Gardham marked PIK3R2 as ready
Malformations of cortical development PIK3R2 Alice Gardham commented on PIK3R2
Malformations of cortical development PIK3R2 Alice Gardham classified PIK3R2 as green
Malformations of cortical development PIK3CA Alice Gardham commented on PIK3CA
Malformations of cortical development PIK3CA Alice Gardham marked PIK3CA as ready
Malformations of cortical development PIK3CA Alice Gardham classified PIK3CA as green
Malformations of cortical development WDR62 Alice Gardham marked WDR62 as ready
Malformations of cortical development WDR62 Alice Gardham classified WDR62 as green
Malformations of cortical development POMT2 Alice Gardham marked POMT2 as ready
Malformations of cortical development POMT2 Alice Gardham commented on POMT2
Malformations of cortical development POMT2 Alice Gardham classified POMT2 as green
Malformations of cortical development POMT1 Alice Gardham marked POMT1 as ready
Malformations of cortical development POMT1 Alice Gardham commented on POMT1
Malformations of cortical development POMT1 Alice Gardham classified POMT1 as green
Malformations of cortical development POMGNT1 Alice Gardham marked POMGNT1 as ready
Malformations of cortical development POMGNT1 Alice Gardham commented on POMGNT1
Malformations of cortical development POMGNT1 Alice Gardham classified POMGNT1 as green
Malformations of cortical development NEDD4L Alice Gardham marked NEDD4L as ready
Malformations of cortical development NEDD4L Alice Gardham commented on NEDD4L
Malformations of cortical development NEDD4L Alice Gardham classified NEDD4L as green
Malformations of cortical development LARGE Alice Gardham marked LARGE as ready
Malformations of cortical development LARGE Alice Gardham commented on LARGE
Malformations of cortical development LARGE Alice Gardham classified LARGE as green
Malformations of cortical development LAMB1 Alice Gardham marked LAMB1 as ready
Malformations of cortical development LAMB1 Alice Gardham classified LAMB1 as green
Malformations of cortical development FKRP Alice Gardham marked FKRP as ready
Malformations of cortical development FKRP Alice Gardham commented on FKRP
Malformations of cortical development FKRP Alice Gardham classified FKRP as green
Malformations of cortical development DYNC1H1 Alice Gardham marked DYNC1H1 as ready
Malformations of cortical development DYNC1H1 Alice Gardham commented on DYNC1H1
Malformations of cortical development DYNC1H1 Alice Gardham classified DYNC1H1 as green
Malformations of cortical development ARFGEF2 Alice Gardham marked ARFGEF2 as ready
Malformations of cortical development ARFGEF2 Alice Gardham classified ARFGEF2 as green
Malformations of cortical development AKT3 Alice Gardham marked AKT3 as ready
Malformations of cortical development AKT3 Alice Gardham commented on AKT3
Malformations of cortical development AKT3 Alice Gardham classified AKT3 as green
Malformations of cortical development ACTG1 Alice Gardham marked ACTG1 as ready
Malformations of cortical development ACTG1 Alice Gardham commented on ACTG1
Malformations of cortical development ACTG1 Alice Gardham classified ACTG1 as green
Malformations of cortical development ACTB Alice Gardham classified ACTB as green
Malformations of cortical development ACTB Alice Gardham commented on ACTB
Malformations of cortical development ACTB Alice Gardham marked ACTB as ready
Malformations of cortical development Ellen McDonagh rejected panel
Malformations of cortical development LARGE Louise Daugherty commented on LARGE
Malformations of cortical development TUBA8 Usha Kini reviewed TUBA8
Malformations of cortical development RELN Usha Kini reviewed RELN
Malformations of cortical development RELN Usha Kini reviewed RELN
Malformations of cortical development LAMB1 Usha Kini added LAMB1 to panel
Malformations of cortical development LAMB1 Usha Kini reviewed LAMB1
Malformations of cortical development LAMC3 Usha Kini reviewed LAMC3
Malformations of cortical development NEDD4L Usha Kini added NEDD4L to panel
Malformations of cortical development NEDD4L Usha Kini reviewed NEDD4L
Malformations of cortical development LARGE Usha Kini added LARGE to panel
Malformations of cortical development LARGE Usha Kini reviewed LARGE
Malformations of cortical development FKRP Usha Kini added FKRP to panel
Malformations of cortical development FKRP Usha Kini reviewed FKRP
Malformations of cortical development POMGNT1 Usha Kini added POMGNT1 to panel
Malformations of cortical development POMGNT1 Usha Kini reviewed POMGNT1
Malformations of cortical development POMT2 Usha Kini added POMT2 to panel
Malformations of cortical development POMT2 Usha Kini reviewed POMT2
Malformations of cortical development POMT1 Usha Kini added POMT1 to panel
Malformations of cortical development POMT1 Usha Kini reviewed POMT1
Malformations of cortical development KIF5C Usha Kini reviewed KIF5C
Malformations of cortical development KIF2A Usha Kini reviewed KIF2A
Malformations of cortical development WDR62 Usha Kini added WDR62 to panel
Malformations of cortical development WDR62 Usha Kini reviewed WDR62
Malformations of cortical development PIK3R2 Usha Kini added PIK3R2 to panel
Malformations of cortical development PIK3R2 Usha Kini reviewed PIK3R2
Malformations of cortical development AKT3 Usha Kini added AKT3 to panel
Malformations of cortical development AKT3 Usha Kini reviewed AKT3
Malformations of cortical development PIK3CA Usha Kini added PIK3CA to panel
Malformations of cortical development PIK3CA Usha Kini reviewed PIK3CA
Malformations of cortical development ARFGEF2 Usha Kini added ARFGEF2 to panel
Malformations of cortical development ARFGEF2 Usha Kini reviewed ARFGEF2
Malformations of cortical development ACTG1 Usha Kini added ACTG1 to panel
Malformations of cortical development ACTG1 Usha Kini reviewed ACTG1
Malformations of cortical development ACTB Usha Kini added ACTB to panel
Malformations of cortical development ACTB Usha Kini reviewed ACTB
Malformations of cortical development DYNC1H1 Usha Kini added DYNC1H1 to panel
Malformations of cortical development DYNC1H1 Usha Kini reviewed DYNC1H1
Malformations of cortical development Sarah Leigh promoted panel to version 1
Malformations of cortical development KATNB1 Sarah Leigh classified KATNB1 as green
Malformations of cortical development KATNB1 Sarah Leigh classified KATNB1 as green
Malformations of cortical development KATNB1 Sarah Leigh marked KATNB1 as ready
Malformations of cortical development KATNB1 Sarah Leigh commented on KATNB1
Malformations of cortical development RELN Sarah Leigh marked RELN as ready
Malformations of cortical development RELN Sarah Leigh classified RELN as red
Malformations of cortical development RELN Sarah Leigh commented on RELN
Malformations of cortical development TUBA1A Sarah Leigh marked TUBA1A as ready
Malformations of cortical development TUBA1A Sarah Leigh commented on TUBA1A
Malformations of cortical development TUBA1A Sarah Leigh classified TUBA1A as green
Malformations of cortical development FLNA Sarah Leigh classified FLNA as green
Malformations of cortical development NDE1 Sarah Leigh marked NDE1 as ready
Malformations of cortical development NDE1 Sarah Leigh commented on NDE1
Malformations of cortical development NDE1 Sarah Leigh classified NDE1 as green
Malformations of cortical development FLNA Sarah Leigh classified FLNA as green
Malformations of cortical development FLNA Sarah Leigh marked FLNA as ready
Malformations of cortical development FLNA Sarah Leigh commented on FLNA
Malformations of cortical development DCX Sarah Leigh marked DCX as ready
Malformations of cortical development DCX Sarah Leigh commented on DCX
Malformations of cortical development DCX Sarah Leigh classified DCX as green
Malformations of cortical development ARX Sarah Leigh marked ARX as ready
Malformations of cortical development ARX Sarah Leigh commented on ARX
Malformations of cortical development ARX Sarah Leigh classified ARX as green
Malformations of cortical development PAFAH1B1 Sarah Leigh marked PAFAH1B1 as ready
Malformations of cortical development PAFAH1B1 Sarah Leigh commented on PAFAH1B1
Malformations of cortical development ADGRG1 Sarah Leigh marked ADGRG1 as ready
Malformations of cortical development ADGRG1 Sarah Leigh commented on ADGRG1
Malformations of cortical development ADGRG1 Sarah Leigh classified ADGRG1 as green
Malformations of cortical development TUBA1A Ian Berry reviewed TUBA1A
Malformations of cortical development NDE1 Ian Berry reviewed NDE1
Malformations of cortical development FLNA Ian Berry reviewed FLNA
Malformations of cortical development DCX Ian Berry reviewed DCX
Malformations of cortical development ARX Ian Berry reviewed ARX
Malformations of cortical development ADGRG1 Ian Berry reviewed ADGRG1