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| 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 |
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| 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 v2.141 | 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 |
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| 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 v2.76 | 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. |
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| 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. |
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| 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 v2.21 | 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 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 v1.152 | 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 |
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| 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 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||