Mutations in mammalian target of rapamycin regulator DEPDC5 cause focal epilepsy with brain malformations. Issue 5 (14th April 2014)

• Record Type: Journal Article
• Authors: 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.
• Is Part Of: Annals of neurology. Volume 75:Issue 5(2014:May)
• Page Start: 782
• Page End: 787
• Publication Date: 2014-04-14
• Subjects: Neurology -- Periodicals; Pediatric neurology -- Periodicals; Nervous system -- Surgery -- Periodicals; 616.8
• DOI: 10.1002/ana.24126
• Languages: English
• ISSNs: 0364-5134

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>We recently identified <italic>DEPDC5</italic> as the gene for familial focal epilepsy with variable foci and found mutations in &gt;10% of small families with nonlesional focal epilepsy. Here we show that <italic>DEPDC5</italic> mutations are associated with both lesional and nonlesional epilepsies, even within the same family. <italic>DEPDC5</italic>‐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 <italic>DEPDC5</italic> mutations share features with the archetypal mTORopathy, tuberous sclerosis, raising the possibility of therapies targeted to this pathway. Ann Neurol 2014;75:782–787</p> </abstract>