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Mutations in mammalian target of rapamycin regulator DEPDC5 cause focal epilepsy with brain malformations
Author(s) -
Scheffer Ingrid E.,
Heron Sarah E.,
Regan Brigid M.,
Mandelstam Simone,
Crompton Douglas E.,
Hodgson Bree L.,
Licchetta Laura,
Provini Federica,
Bisulli Francesca,
Vadlamudi Lata,
Gecz Jozef,
Connelly Alan,
Tinuper Paolo,
Ricos Michael G.,
Berkovic Samuel F.,
Dibbens Leanne M.
Publication year - 2014
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.24126
Subject(s) - tuberous sclerosis , cortical dysplasia , epilepsy , phenotype , dysplasia , regulator , hippocampal sclerosis , neuroscience , biology , cancer research , tsc1 , pi3k/akt/mtor pathway , sirolimus , medicine , pathology , genetics , signal transduction , gene , temporal lobe
We recently identified DEPDC5 as the gene for familial focal epilepsy with variable foci and found mutations in >10% of small families with nonlesional focal epilepsy. Here we show that DEPDC5 mutations are associated with both lesional and nonlesional epilepsies, even within the same family. DEPDC5 ‐associated malformations include bottom‐of‐the‐sulcus dysplasia (3 members from 2 families), and focal band heterotopia (1 individual). DEPDC5 negatively regulates the mammalian target of rapamycin (mTOR) pathway, which plays a key role in cell growth. The clinicoradiological phenotypes associated with DEPDC5 mutations share features with the archetypal mTORopathy, tuberous sclerosis, raising the possibility of therapies targeted to this pathway. Ann Neurol 2014;75:782–787