Familial cortical dysplasia type IIA caused by a germline mutation in DEPDC5
نویسندگان
چکیده
Whole-exome sequencing of two brothers with drug-resistant, early-onset, focal epilepsy secondary to extensive type IIA focal cortical dysplasia identified a paternally inherited, nonsense variant of DEPDC5 (c.C1663T, p.Arg555*). This variant has previously been reported to cause familial focal epilepsy with variable foci in patients with normal brain imaging. Immunostaining of resected brain tissue from both brothers demonstrated mammalian target of rapamycin (mTOR) activation. This report shows the histopathological features of cortical dysplasia associated with a DEPDC5 mutation, confirms mTOR dysregulation in the malformed tissue and expands the spectrum of neurological manifestations of DEPDC5 mutations to include severe phenotypes with large areas of cortical malformation.
منابع مشابه
Familial focal epilepsy with focal cortical dysplasia due to DEPDC5 mutations.
OBJECTIVE The DEPDC5 (DEP domain-containing protein 5) gene, encoding a repressor of the mTORC1 signaling pathway, has recently emerged as a major gene mutated in familial focal epilepsies. We aimed to further extend the role of DEPDC5 to focal cortical dysplasias (FCDs). METHODS Seven patients from 4 families with DEPDC5 mutations and focal epilepsy associated with FCD were recruited and inv...
متن کاملTwo definite cases of sudden unexpected death in epilepsy in a family with a DEPDC5 mutation
The DEPDC5 gene (OMIM #614191), mapped to 22q12.2-q12.3, encodes the DEP domain-containing protein 5. DEPDC5 has been associated with a variety of familial epilepsies, including familial focal epilepsy with variable foci, autosomal dominant nocturnal frontal lobe epilepsy, familial temporal lobe epilepsy, epileptic spasms, and cortical dysplasia.(1-4) Notably, DEPDC5 has never been linked to in...
متن کاملmTOR pathway in familial focal epilepsies
An increasingly recognized role of genes encoding components of the mammalian Target Of Rapamycin (mTOR) signal transduction pathway has recently emerged among familial focal epilepsies. Loss-of-function mutations in the Dishevelled, Egl-10 and Pleckstrin Domain Containing protein 5 (DEPDC5) gene, and lately in the genes encoding Nitrogen Permease Regulator Like 2 and 3 proteins (NPRL2 and NPRL...
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OBJECTIVE To assess the presence of DEPDC5 mutations in a cohort of patients with epileptic spasms. METHODS We performed DEPDC5 resequencing in 130 patients with spasms, segregation analysis of variants of interest, and detailed clinical assessment of patients with possibly and likely pathogenic variants. RESULTS We identified 3 patients with variants in DEPDC5 in the cohort of 130 patients...
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DEP-domain containing 5 (DEPDC5), encoding a repressor of the mechanistic target of rapamycin complex 1 (mTORC1) signaling pathway, has recently emerged as a major gene mutated in familial focal epilepsies and focal cortical dysplasia. Here we established a global knockout rat using TALEN technology to investigate in vivo the impact of Depdc5-deficiency. Homozygous Depdc5(-/-) embryos died from...
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عنوان ژورنال:
دوره 2 شماره
صفحات -
تاریخ انتشار 2015