Mammalian Target of Rapamycin Pathway Mutations Cause Hemimegalencephaly and Focal Cortical Dysplasia

被引：218

作者：

D'Gama, Alissa M. ^{[1
,2
,3
,4
,5
,6
]}

Geng, Ying ^{[1
,2
,3
,4
,5
,6
]}

Couto, Javier A. ^{[7
]}

Martin, Beth ^{[8
]}

Boyle, Evan A. ^{[8
]}

LaCoursiere, Christopher M. ^{[9
]}

Hossain, Amer ^{[1
,2
,3
,4
,5
,6
]}

Hatem, Nicole E. ^{[1
,2
,3
,4
,5
,6
]}

Barry, Brenda J. ^{[1
,2
,3
,4
,5
,6
]}

Kwiatkowski, David J. ^{[10
]}

Vinters, Harry V. ^{[11
]}

Barkovich, A. James ^{[12
]}

Shendure, Jay ^{[8
]}

Mathern, Gary W. ^{[13
,14
,15
]}

Walsh, Christopher A. ^{[1
,2
,3
,4
,5
,6
]}

Poduri, Annapurna ^{[9
,16
]}

机构：

[1] Boston Childrens Hosp, Manton Ctr Orphan Dis Res, Dept Med, Div Genet & Genom, Boston, MA 02115 USA

[2] Boston Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA

[3] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA

[4] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA

[5] Broad Inst Massachusetts Inst Technol, Program Med & Populat Genet, Cambridge, MA USA

[6] Harvard Univ, Cambridge, MA 02138 USA

[7] Harvard Univ, Sch Med, Plast & Oral Surg Dept, Boston Childrens Hosp, Boston, MA 02115 USA

[8] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA

[9] Harvard Univ, Sch Med, Dept Neurol, Boston Childrens Hosp, Boston, MA 02115 USA

[10] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA

[11] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA

[12] Univ Calif San Francisco, Dept Neuroradiol, Pediat Neuroradiol, San Francisco, CA 94143 USA

[13] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurosurg, Mattel Childrens Hosp, Los Angeles, CA USA

[14] Univ Calif Los Angeles, David Geffen Sch Med, Mattel Childrens Hosp, Dept Psychiat, Los Angeles, CA 90095 USA

[15] Univ Calif Los Angeles, David Geffen Sch Med, Mattel Childrens Hosp, Dept Biobehav Med, Los Angeles, CA 90095 USA

[16] Boston Childrens Hosp, Epilepsy Genet Program, Div Epilepsy & Clin Neurophysiol, Dept Neurol, Boston, MA 02115 USA

来源：

ANNALS OF NEUROLOGY | 2015年 / 77卷 / 04期

关键词：

BRAIN MALFORMATIONS; SOMATIC MUTATIONS; PIK3CA CAUSE; AKT3; EPILEPSY; DEPDC5;

D O I：

10.1002/ana.24357

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

Focal malformations of cortical development, including focal cortical dysplasia (FCD) and hemimegalencephaly (HME), are important causes of intractable childhood epilepsy. Using targeted and exome sequencing on DNA from resected brain samples and nonbrain samples from 53 patients with FCD or HME, we identified pathogenic germline and mosaic mutations in multiple PI3K/AKT pathway genes in 9 patients, and a likely pathogenic variant in 1 additional patient. Our data confirm the association of DEPDC5 with sporadic FCD but also implicate this gene for the first time in HME. Our findings suggest that modulation of the mammalian target of rapamycin pathway may hold promise for malformation-associated epilepsy. Ann Neurol 2015;77:720-725

引用

页码：720 / 725

页数：6

共 22 条

[21] Duplication AKT3 as a Cause of Macrocephaly in Duplication 1q43q44
Wang, David
Zeesman, Susan
Tarnopolsky, Mark A.
Nowaczyk, Malgorzata J. M.
[J]. AMERICAN JOURNAL OF MEDICAL GENETICS PART A, 2013, 161 (08) : 2016 - 2019
[22] Using Whole-Exome Sequencing to Identify Inherited Causes of Autism
Yu, Timothy W.
Chahrour, Maria H.
Coulter, Michael E.
Jiralerspong, Sarn
Okamura-Ikeda, Kazuko
Ataman, Bulent
Schmitz-Abe, Klaus
Harmin, David A.
Adli, Mazhar
Malik, Athar N.
D'Gama, Alissa M.
Lim, Elaine T.
Sanders, Stephan J.
Mochida, Ganesh H.
Partlow, Jennifer N.
Sunu, Christine M.
Felie, Jillian M.
Rodriguez, Jacqueline
Nasir, Ramzi H.
Ware, Janice
Joseph, Robert M.
Hill, R. Sean
Kwan, Benjamin Y.
Al-Saffar, Muna
Mukaddes, Nahit M.
Hashmi, Asif
Balkhy, Soher
Gascon, Generoso G.
Hisama, Fuki M.
LeClair, Elaine
Poduri, Annapurna
Oner, Ozgur
Al-Saad, Samira
Al-Awadi, Sadika A.
Bastaki, Laila
Ben-Omran, Tawfeg
Teebi, Ahmad S.
Al-Gazali, Lihadh
Eapen, Valsamma
Stevens, Christine R.
Rappaport, Leonard
Gabriel, Stacey B.
Markianos, Kyriacos
State, Matthew W.
Greenberg, Michael E.
Taniguchi, Hisaaki
Braverman, Nancy E.
Morrow, Eric M.
Walsh, Christopher A.
[J]. NEURON, 2013, 77 (02) : 259 - 273

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