Association of a synonymous SCN1B variant affecting splicing efficiency with Benign Familial Infantile Epilepsy (BFIE)

Item Type:	Article
Title:	Association of a synonymous SCN1B variant affecting splicing efficiency with Benign Familial Infantile Epilepsy (BFIE)
Creators Name:	Usluer, S. and Kayserili, M.A. and Eken, A.G. and Yiş, U. and Leu, C. and Altmüller, J. and Thiele, H. and Nürnberg, P. and Sander, T. and Çağlayan, S.H.
Abstract:	Benign Familial Infantile Epilepsy (BFIE) is clinically characterized by clusters of brief partial seizures progressing to secondarily generalized seizures with onset at the age of 3–7 months and with favorable outcome. PRRT2 mutations are the most common cause of BFIE, and found in about 80% of BFIE families. In this study, we analyzed a large multiplex BFIE family by linkage and whole exome sequencing (WES) analyses. Genome-wide linkage analysis revealed significant evidence for linkage in the chromosomal region 19p12-q13 (LOD score 3.48). Mutation screening of positional candidate genes identified a synonymous SCN1B variant (c.492T>C, p.Tyr164Tyr) affecting splicing by the removal of a splicing silencer sequence, shown by in silico analysis, as the most likely causative mutation. In addition, the PRRT2 frameshift mutation (c.649dupC/p.Arg217Profs*8) was observed, showing incomplete, but high segregation with the phenotype. In vitro splicing assay of SCN1B expression confirmed the in silico findings showing a splicing imbalance between wild type and mutant exons. Herein, the involvement of the SCN1B gene in the etiology of BFIE, contributing to the disease phenotype as a modifier or part of an oligogenic predisposition, is shown for the first time.
Keywords:	Benign Familial Infantile Epilepsy (BFIE), SCN1B, PRRT2, Splice Variant, Minigene Reporter Assay
Source:	European Journal of Paediatric Neurology
ISSN:	1090-3798
Publisher:	Elsevier
Volume:	21
Number:	5
Page Range:	773-782
Date:	September 2017
Official Publication:	https://doi.org/10.1016/j.ejpn.2017.05.001
PubMed:	View item in PubMed

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