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Familial cortical dysplasia caused by mutation in the mammalian target of rapamycin regulator NPRL3
Author(s) -
Sim Joe C.,
Scerri Thomas,
FanjulFernández Miriam,
Riseley Jessica R.,
Gillies Greta,
Pope Kate,
van Roozendaal Hanna,
Heng Julian I.,
Mandelstam Simone A.,
McGillivray George,
MacGregor Duncan,
Kannan Lakshminarayanan,
Maixner Wirginia,
Harvey A. Simon,
Amor David J.,
Delatycki Martin B.,
Crino Peter B.,
Bahlo Melanie,
Lockhart Paul J.,
Leventer Richard J.
Publication year - 2016
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.24502
Subject(s) - cortical dysplasia , regulator , frameshift mutation , germline , biology , exome sequencing , germline mutation , genetics , mutation , immunostaining , epilepsy , cancer research , gene , neuroscience , immunohistochemistry , immunology
We describe first cousin sibling pairs with focal epilepsy, one of each pair having focal cortical dysplasia (FCD) IIa. Linkage analysis and whole‐exome sequencing identified a heterozygous germline frameshift mutation in the gene encoding nitrogen permease regulator‐like 3 ( NPRL3) . NPRL3 is a component of GAP Activity Towards Rags 1, a negative regulator of the mammalian target of rapamycin complex 1 signaling pathway. Immunostaining of resected brain tissue demonstrated mammalian target of rapamycin activation. Screening of 52 unrelated individuals with FCD identified 2 additional patients with FCDIIa and germline NPRL3 mutations. Similar to DEPDC5 , NPRL3 mutations may be considered as causal variants in patients with FCD or magnetic resonance imaging–negative focal epilepsy. ANN NEUROL 2016;79:132–137