Al-Mehmadi Sameer, Splitt Miranda, Ramesh Venkateswaran, DeBrosse Suzanne, Dessoffy Kimberly, Xia Fan, Yang Yaping, Rosenfeld Jill A, Cossette Patrick, Michaud Jacques L, Hamdan Fadi F, Campeau Philippe M, Minassian Berge A
Program in Genetics and Genome Biology and Division of Neurology (S.A.-M., B.A.M.), Department of Paediatrics, The Hospital for Sick Children, and University of Toronto, Ontario, Canada; Institute of Genetic Medicine (M.S.), International Centre for Life, Pediatric Neurology (V.R.), Newcastle General Hospital, UK; Center for Human Genetics (S.D., K.D.), UH Case Medical Center, Cleveland, OH; Department of Molecular and Human Genetics (F.X., Y.Y., J.A.R.), Baylor College of Medicine, Houston, TX; Baylor Miraca Genetics Laboratories (F.X., Y.Y.), Houston, TX; The Deciphering Developmental Disorders (DDD) Study, Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK; Division of Neurology (P.C.), CHUM Notre-Dame, Hospital University of Montreal, Quebec, Canada; Department of Pediatrics (J.L.M., P.M.C.), Department of Neurosciences (J.L.M., P.M.C.), Université de Montréal, Québec, Canada; and CHU Sainte-Justine Research Center (J.L.M., F.A.H., P.M.C.), Montreal, Quebec, Canada.
Neurol Genet. 2016 Oct 28;2(6):e115. doi: 10.1212/NXG.0000000000000115. eCollection 2016 Dec.
Voltage-gated sodium channels (Nas) are mainstays of neuronal function, and mutations in the genes encoding CNS Nas (Na1.1 [], Na1.2 [], Na1.3 [], and Na1.6 []) are causes of some of the most common and severe genetic epilepsies and epileptic encephalopathies (EE). Fibroblast-growth-factor homologous factors (FHFs) compose a family of 4 proteins that interact with the C-terminal tails of Nas to modulate the channels' fast, and long-term, inactivations. mutation is a rare cause of generalized epilepsy with febrile seizures plus (GEFS+). Recently, a de novo mutation (p.R52H) was reported in early-onset EE in 2 siblings. We report 3 patients from unrelated families with the same p.R52H mutation. The 5 cases together frame the FHF1 R52H EE from infancy to adulthood. As discussed below, this gain-of-function disease may be amenable to personalized therapy.
电压门控钠通道（Nas）是神经元功能的支柱，编码中枢神经系统Nas（Na1.1 []、Na1.2 []、Na1.3 []和Na1.6 []）的基因突变是一些最常见和严重的遗传性癫痫及癫痫性脑病（EE）的病因。成纤维细胞生长因子同源因子（FHFs）由4种蛋白质组成的家族，它们与Nas的C末端尾巴相互作用，以调节通道的快速和长期失活。突变是伴有热性惊厥附加症的全身性癫痫（GEFS+）的罕见病因。最近，在2名同胞的早发性EE中报告了一种新发突变（p.R52H）。我们报告了来自无关家族的3例具有相同p.R52H突变的患者。这5例病例共同勾勒出了从婴儿期到成年期的FHF1 R52H EE。如下所述，这种功能获得性疾病可能适合个性化治疗。
