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| Malformations of cortical development v4.8 | DEPDC5 | Achchuthan Shanmugasundram Tag Q1_23_MOI was removed from gene: DEPDC5. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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 | 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 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. |
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| 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 | DEPDC5 | Arina Puzriakova Tag Q3_21_rating was removed from gene: DEPDC5. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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 v3.10 | 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) |
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| 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 v2.11 | 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 |
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