Journal article
Familial cortical dysplasia caused by mutation in the mammalian target of rapamycin regulator NPRL3
JC Sim, T Scerri, M Fanjul-Fernández, JR Riseley, G Gillies, K Pope, H Van Roozendaal, JI Heng, SA Mandelstam, G McGillivray, D Macgregor, L Kannan, W Maixner, AS Harvey, DJ Amor, MB Delatycki, PB Crino, M Bahlo, PJ Lockhart, RJ Leventer
Annals of Neurology | Published : 2016
DOI: 10.1002/ana.24502
Abstract
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 cau..
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Awarded by National Institutes of Health
Funding Acknowledgements
This work has been supported by the Victorian Government's Operational Infrastructure Support Program and Australian Government NHMRC IRIISS. Funding was provided by the National Health and Medical Research Council of Australia, the Murdoch Childrens Research Institute, and the Campbell Edwards Trust. M.B. is supported by an NHMRC Senior Research Fellowship (APP1002098) and an NHMRC Program Grant (APP1054618). P.B.C. is supported by NINDS R01NS082343-01. We thank the families for participating in this study. We are grateful for the generous support of the Lefroy and Handbury families.