Early onset or syndromic epilepsy

Gene: DEPDC5

The mode of inheritance of this gene has been updated to BOTH monoallelic and biallelic, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.

Created: 11 Oct 2023, 11:59 a.m. | Last Modified: 11 Oct 2023, 11:59 a.m.

Panel Version: 4.110

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Green List (high evidence)

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'.

Created: 8 Mar 2023, 4:32 p.m. | Last Modified: 8 Mar 2023, 4:32 p.m.

Panel Version: 3.104

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. 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.

Created: 8 Mar 2023, 4:17 p.m. | Last Modified: 8 Mar 2023, 4:17 p.m.

Panel Version: 3.102

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Epilepsy, familial focal, with variable foci 1, OMIM:604364; epilepsy, MONDO:0005027; Macrocephaly, HP:0000256; polymicrogyria, MONDO:0000087; neurodevelopmental disorder, MONDO:0700092

Publications

• 32848577
• 36067010

I don't know

Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: John Taylor and Helen Lord. Suggested gene rating: Green.

Created: 6 Aug 2019, 8:38 p.m. | Last Modified: 6 Aug 2019, 8:38 p.m.

Panel Version: 1.189

Green List (high evidence)

AD familial focal epliepsy with variable foci 1 (FFEVF) - characterised by focal seizures arising from different cortical regions in diff family members - this disorder shows incomplete penetrance. Xiong et al, 1999 - 2 lge French Canadian families - segregating a familial partial epilepsy synd with variable foci. Callenbach et al, 2003 - 4 generation Dutch family - 12 individuals had epilepsy consistent with FFEVF. Berkovic et al, 2004 - 5 gen Spanish family - 14 individuals partial seizures - Dibbens et al, 2013 reported het mutations in the cases described by the first 3 papers. Ishida et al, 2013 - 6 unrelated families with AD focal epilepsy - 6 diff het variants - 5 result in truncated protein. Picard et al, 2014 - 9 patients from 4 unrelated families with FFEVF - 4 diff het mutations identified. Two unaff members also carriers indicating incomplete penetrance. No functional work done. Schaffer et al, 2014 - 6 aff members of an Australian family - het truncating mutation.

Created: 6 Aug 2019, 8:31 p.m. | Last Modified: 6 Aug 2019, 8:31 p.m.

Panel Version: 1.188

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Epilepsy, familial focal, with variable foci 1,604364

Publications

• 9851433
• 23542697

Green List (high evidence)

Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 12 variants reported

Created: 9 Apr 2018, 9:41 a.m.

Red List (low evidence)

Red List (low evidence)

Red List (low evidence)

Red List (low evidence)

Green List (high evidence)

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
604364

Publications

• 14510823
• 15329069
• 10825362
• 10577924
• 9851433
• 23542701