Familial cortical dysplasia caused by mutation in the mammalian target of rapamycin regulator NPRL3

J.C. Sim, T. Scerri, M. Fanjul-Fernández, J.R. Riseley, G. Gillies, K. Pope, H. Van Roozendaal, Julian Heng, S.A. Mandelstam, G. Mcgillivray, D. Macgregor, L. Kannan, W. Maixner, A.S. Harvey, D.J. Amor, M.B. Delatycki, P.B. Crino, M. Bahlo, P.J. Lockhart, R.J. Leventer

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92 Citations (Scopus)

Abstract

© 2015 American Neurological Association. 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.
Original languageEnglish
Pages (from-to)132-137
Number of pages6
JournalAnnals of Neurology
Volume79
Issue number1
Early online date12 Dec 2015
DOIs
Publication statusPublished - 1 Jan 2016

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