Open AccessFamilial cortical dysplasia type IIA caused by a germline mutation in DEPDC 5
Author(s) -
Scerri Thomas,
Riseley Jessica R.,
Gillies Greta,
Pope Kate,
Burgess Rosemary,
Mandelstam Simone A.,
Dibbens Leanne,
Chow Chung W.,
Maixner Wirginia,
Harvey Anthony Simon,
Jackson Graeme D.,
Amor David J.,
Delatycki Martin B.,
Crino Peter B.,
Berkovic Samuel F.,
Scheffer Ingrid E.,
Bahlo Melanie,
Lockhart Paul J.,
Leventer Richard J.
Publication year - 2015
Publication title -
annals of clinical and translational neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.824
H-Index - 42
ISSN - 2328-9503
DOI - 10.1002/acn3.191
Subject(s) - cortical dysplasia , medicine , nonsense mutation , exome sequencing , epilepsy , phenotype , germline , immunostaining , germline mutation , mutation , nonsense , pathology , dysplasia , cancer research , immunohistochemistry , genetics , biology , missense mutation , gene , psychiatry
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 DEPDC 5 (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 DEPDC 5 mutation, confirms mTOR dysregulation in the malformed tissue and expands the spectrum of neurological manifestations of DEPDC 5 mutations to include severe phenotypes with large areas of cortical malformation.