Mutations in Mammalian Target of Rapamycin Regulator DEPDC5 Cause Focal Epilepsy with Brain Malformations

被引：194

作者：

Scheffer, Ingrid E. ^{[1
,2
,3
]}

Heron, Sarah E. ^{[4
,5
]}

Regan, Brigid M. ^{[1
]}

Mandelstam, Simone ^{[2
,3
,6
]}

Crompton, Douglas E. ^{[7
]}

Hodgson, Bree L. ^{[4
,5
]}

Licchetta, Laura ^{[8
]}

Provini, Federica ^{[8
,9
]}

Bisulli, Francesca ^{[8
,9
]}

Vadlamudi, Lata ^{[1
,10
,11
]}

Gecz, Jozef ^{[12
]}

Connelly, Alan ^{[2
,13
]}

Tinuper, Paolo ^{[8
,9
]}

Ricos, Michael G. ^{[4
,5
]}

Berkovic, Samuel F. ^{[1
]}

Dibbens, Leanne M. ^{[4
,5
]}

机构：

[1] Univ Melbourne, Dept Med, Epilepsy Res Ctr, Austin Hlth, Melbourne, Vic, Australia

[2] Florey Inst Neurosci & Mental Hlth, Melbourne, Vic, Australia

[3] Univ Melbourne, Royal Childrens Hosp, Dept Paediat, Melbourne, Vic, Australia

[4] Univ S Australia, Epilepsy Res Program, Sch Pharm & Med Sci, Adelaide, SA 5000, Australia

[5] Univ S Australia, Sansom Inst Hlth Res, Adelaide, SA 5000, Australia

[6] Univ Melbourne, Royal Childrens Hosp, Dept Radiol, Melbourne, Vic, Australia

[7] Northern Hlth, Dept Neurol, Melbourne, Vic, Australia

[8] Univ Bologna, IRCCS, Inst Neurol Sci, Bologna, Italy

[9] Univ Bologna, Dept Biomed & Neuromotor Sci, Bologna, Italy

[10] Univ Queensland, Sch Med, Brisbane, Qld, Australia

[11] Royal Brisbane & Womens Hosp, Dept Neurol, Brisbane, Qld, Australia

[12] Univ Adelaide, Sch Paediat & Reprod Hlth, Adelaide, SA, Australia

[13] Univ Melbourne, Austin Hlth, Dept Med, Melbourne, Vic, Australia

来源：

ANNALS OF NEUROLOGY | 2014年 / 75卷 / 05期

基金：

澳大利亚研究理事会; 英国医学研究理事会;

关键词：

VARIABLE FOCI; CLASSIFICATION; HAMARTOMAS; LESIONS; COMPLEX; BOTTOM; SULCUS;

D O I：

10.1002/ana.24126

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

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.

引用

页码：782 / 787

页数：6

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