Universität zu Köln

Usluer, Sunay, Kayserili, Melek Asli, Eken, Asli Gundogdu, Yis, Uluc, Leu, Costin ORCID: 0000-0003-0598-3301, Altmueller, Janine, Thiele, Holger, Nuernberg, Peter, Sander, Thomas and Caglayan, S. Hande (2017). Association of a synonymous SCN1B variant affecting splicing efficiency with Benign Familial Infantile Epilepsy (BFIE). Eur. J. Paediatr. Neurol., 21 (5). S. 773 - 783. OXFORD: ELSEVIER SCI LTD. ISSN 1532-2130

Full text not available from this repository.

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. (C) 2017 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Usluer, Sunay UNSPECIFIED UNSPECIFIED UNSPECIFIED Kayserili, Melek Asli UNSPECIFIED UNSPECIFIED UNSPECIFIED Eken, Asli Gundogdu UNSPECIFIED UNSPECIFIED UNSPECIFIED Yis, Uluc UNSPECIFIED UNSPECIFIED UNSPECIFIED Leu, Costin UNSPECIFIED orcid.org/0000-0003-0598-3301 UNSPECIFIED Altmueller, Janine UNSPECIFIED UNSPECIFIED UNSPECIFIED Thiele, Holger UNSPECIFIED UNSPECIFIED UNSPECIFIED Nuernberg, Peter UNSPECIFIED UNSPECIFIED UNSPECIFIED Sander, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Caglayan, S. Hande UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-220132
DOI:	10.1016/j.ejpn.2017.05.001
Journal or Publication Title:	Eur. J. Paediatr. Neurol.
Volume:	21
Number:	5
Page Range:	S. 773 - 783
Date:	2017
Publisher:	ELSEVIER SCI LTD
Place of Publication:	OXFORD
ISSN:	1532-2130
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CHILDHOOD ABSENCE EPILEPSY; BRUGADA-SYNDROME; CONVULSIONS; MUTATION; LINKAGE; PRRT2; IDENTIFICATION; SUBUNIT; GENES Multiple languages Clinical Neurology; Pediatrics Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/22013