Research panel - Severe Paediatric Disorders
Gene: DEPDC5

DEPDC5 (DEP domain containing 5)
EnsemblGeneIds (GRCh38): ENSG00000100150
EnsemblGeneIds (GRCh37): ENSG00000100150
OMIM: 614191, Gene2Phenotype
DEPDC5 is in 5 panels

2 reviews

Achchuthan Shanmugasundram (Genomics England Curator)

Green List (high evidence)

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.
Created: 8 Mar 2023, 4:35 p.m. | Last Modified: 8 Mar 2023, 4:35 p.m.

Panel Version: 1.147

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; cerebral cortical dysplasia, MONDO:0017094; neurodevelopmental disorder, MONDO:0700092

Publications

Created: 8 Mar 2023, 4:35 p.m.
Last Modified: 8 Mar 2023, 4:35 p.m.
Panel version: 1.147

Louise Daugherty (Genomics England Curator)

I don't know

Initial gene list (NGC_genelist-20190823_GREEN_dis_moi_forCuration_20200211.xlsx) collated by Dr Courtney French (University of Cambridge University Hospital NHS Foundation), Dr Karyn Megy (Clinical Feedback Lead, NIHR BioResource - Rare Diseases Study, University of Cambridge University Hospital NHS Foundation), Dr Alba Sanchis-Juan (NIHR BioResource - Rare Diseases Study, University of Cambridge University Hospital NHS Foundation) and Lucy Raymond (Professor of Medical Genetics and Neurodevelopment, University of Cambridge University Hospital NHS Foundation). Submitted to the PanelApp resource January 2020 on behalf of the Next Generation Children Project, Addenbrookes' Hospital, Cambridge. Gene Symbol submitted: DEPDC5; Recommended initial gene rating: Green List (high evidence); Phenotypes: Epilepsy, familial focal, with variable foci 1, 604364 (3); Mode of inheritance: Autosomal dominant
Created: 20 Feb 2020, 5:18 p.m. | Last Modified: 20 Feb 2020, 5:18 p.m.

Panel Version: 0.12

Created: 20 Feb 2020, 5:18 p.m.
Last Modified: 20 Feb 2020, 5:18 p.m.
Panel version: 0.12

Details

Mode of Inheritance

MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Sources

Next Generation Children Project
Expert Review Green
Expert list

Phenotypes

Epilepsy, familial focal, with variable foci 1, 604364

OMIM

614191

Clinvar variants

Variants in DEPDC5

Penetrance

None

Publications

30847515

Panels with this gene