DEPDC5 was first reported in families of individuals with autosomal dominant focal epilepsy in 2013 (Dibbens et al., PMID: 23542697). Seven variants that have been observed in 8 probands in 3 publications are included in this curation (PMIDs: 23542697, 23542701, 24283814). Variants in this gene segregated with disease in at least 48 additional family members (PMID: 23542697). Of note, variants in this gene have been found to exhibit reduced penetrance in families with disease and may present with variable foci across affected family members (PMIDs: 23542697, 24283814, 23542701). More evidence is available in the literature, but the maximum score for genetic evidence (12 pts.) has been reached. The mechanism for disease is thought to be haploinsufficiency (PMID: 23542697). This gene-disease relationship is also supported by animal models, expression studies, and in vitro cell-culture assays (PMIDs: 29761115, 29861134, 29950950, 29708509, 29481864). In summary, there is definitive evidence supporting the relationship between DEPDC5 and autosomal dominant focal epilepsy (MONDO:0005384). This has been repeatedly demonstrated in both the research and clinical diagnostic settings, and has been upheld over time.
Of note, this gene-disease pair was originally evaluated by the ClinGen Epilepsy Gene Curation Expert Panel on August 7, 2018. As of January 11, 2023, this record underwent administrative updates to re-enter evidence according to SOP Version 9, and to update the disease term from familial focal epilepsy with variable foci to focal epilepsy. This new disease term aligns with the other curations for genes involved in the GATOR1 protein complex. No new evidence has been reviewed or added.
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