FHF1 (FGF12) epileptic encephalopathy.

Neurol Genet 2016 Dec 28;2(6):e115. Epub 2016 Oct 28.

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.

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.

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http://dx.doi.org/10.1212/NXG.0000000000000115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5087254PMC
December 2016
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