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
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 | ||||||||||||||||||||||||||||||||||||||||||||
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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: |
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Refereed: | Yes | ||||||||||||||||||||||||||||||||||||||||||||
URI: | http://kups.ub.uni-koeln.de/id/eprint/22013 |
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