Nocturnal frontal lobe epilepsy caused by a mutation in the GATOR1 complex gene NPRL3
Nocturnal frontal lobe epilepsy caused by a mutation in the GATOR1 complex gene NPRL3
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DOI：
10.1111/epi.13307
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发表时间：
2016-03-01
期刊：
影响因子：
5.6
通讯作者：
Steinlein, Ortrud K.
中科院分区：
文献类型：
--
作者：
Korenke, Georg-Christoph;Eggert, Marlene;Steinlein, Ortrud K.
NPRL3是编码mtorc1调节GATOR1复合物蛋白的三个基因之一，最近有报道称NPRL3突变可导致局灶性癫痫的皮质发育不良。我们现在通过全外显子组测序分析了一个多重癫痫家族，并在NPRL3的第13外显子内发现了一个移码突变（NM_001077350.2; c.1522delG; p.E508Rfs*46）。这种截断突变导致癫痫表型，其特征是儿童早期发病，主要是夜间额叶癫痫。与离子通道或depdc5相关家族性夜间额叶癫痫的家族相比，我们家族的外显率很低（6个突变携带者中有3个受影响）。没有明显的脑结构异常表明NPRL3突变不一定与局灶性皮质发育不良有关，但可能通过不同的未知病理机制引起癫痫。
Mutations in NPRL3, one of three genes that encode proteins of the mTORC1-regulating GATOR1 complex, have recently been reported to cause cortical dysplasia with focal epilepsy. We have now analyzed a multiplex epilepsy family by whole exome sequencing and identified a frameshift mutation (NM_001077350.2; c.1522delG; p.E508Rfs*46) within exon 13 of NPRL3. This truncating mutation causes an epilepsy phenotype characterized by early childhood onset of mainly nocturnal frontal lobe epilepsy. The penetrance in our family was low (three affected out of six mutation carriers), compared to families with either ion channel- or DEPDC5-associated familial nocturnal frontal lobe epilepsy. The absence of apparent structural brain abnormalities suggests that mutations in NPRL3 are not necessarily associated with focal cortical dysplasia but might be able to cause epilepsy by different, yet unknown pathomechanisms.