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

2016-01

Sim, Joe C

Scerri, Thomas

Fanjul-Fernández, 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

Journal Article

10.1002/ana.24502

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.

link

Annals of neurology 2016; 79(1): 132-7

Annals of neurology