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

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

© 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...

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Bibliographic Details
Main Authors: Sim, J., Scerri, T., Fanjul-Fernández, M., Riseley, J., Gillies, G., Pope, K., Van Roozendaal, H., Heng, Julian, Mandelstam, S., McGillivray, G., Macgregor, D., Kannan, L., Maixner, W., Harvey, A., Amor, D., Delatycki, M., Crino, P., Bahlo, M., Lockhart, P., Leventer, R.
Format: Journal Article
Published: John Wiley and Son 2016
Online Access:http://hdl.handle.net/20.500.11937/71048
Description
Summary:© 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.

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