alexa Functional Analysis of the C.3705+5G>C Mutation in the
ISSN: 1747-0862

Journal of Molecular and Genetic Medicine
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Research Article

Functional Analysis of the C.3705+5G>C Mutation in the SCN1A Gene: Cryptic Splicing Site Activation and Partial Exon Skipping

Mahmoud AB1*, Fakhfakh F1,2, Mansour RB3, Driss F4, Gargouri SB1, Tabebi M1, Rhouma BB1, Tlili A5 and Siala O1

1Laboratory of Human Molecular Genetics, Faculty of Medicine of Sfax, University of Sfax, Tunisia

2Department of Life Sciences, Faculty of Science of Sfax, University of Sfax, Tunisia

3ISBS (High Institute of Biotechnology of Sfax) Sfax, Tunisia

4CBS (Center of Biotechnology of Sfax) Sfax, Tunisia

5Department of Applied Biology, College of Sciences, University of Sharjah, UAE

*Corresponding Author:
Dr. Afif Ben Mahmoud
Laboratory of Human Molecular Genetics
Faculty of Medicine of Sfax
University of Sfax, Tunisia
Tel: 0021650006062
E-mail: [email protected]

Received date: November 24, 2016; Accepted date: December 05, 2016; Published date: December 08, 2016

Citation: Mahmoud AB, Fakhfakh F, Mansour RB, Driss F, Gargour SB, et al. (2016) Functional Analysis of the C.3705+5G>C Mutation in the SCN1A Gene: Cryptic Splicing Site Activation and Partial Exon Skipping. J Mol Genet Med 10:237 doi:10.4172/1747-0862.1000237

Copyright: © 2016 Mahmoud AB, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

 

Abstract

Several substitutions in Voltage-gated sodium channels (SCN1A) gene have been reported to cause aberrant splicing. Accordingly, this study aimed to investigate the potential effects of a transition in the fifth nucleotide at the donor splice site of intron 18 of the SCN1A gene previously described leading to SIGEI phenotype. Functional analyses using PCR mutagenesis, followed by an ex-vivo splicing assays, revealed that the c.3705+5G>C mutation leads to the activation of a cryptic site into exon 18 leading to a partial exon skipping followed by a premature stop codon at position 1253 in the SCN1A protein. Bioinformatic tools showed an homology between cryptic and normal splicing consensus especially at position - 3, -2, -1, +1, +2 and +5; confirming the crucial role of these positions in the exon definition and explains the strength of the novel donor consensus. This analysis revealed also the enrichment of regions close to the new splice site in ESEs elements with high scores underlining the importance of ESEmediated SR protein function for accurate new splice site recognition. Our results demonstrate that splicing analysis of mRNA may help to understand both the functional consequences of mutations affected splicing consensus and the correlation between genotype and phenotype.

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