Počet záznamů: 1
Clinical, in silico, and experimental evidence for pathogenicity of two novel splice site mutations in the SH3TC2 gene
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SYSNO ASEP 0386622 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Clinical, in silico, and experimental evidence for pathogenicity of two novel splice site mutations in the SH3TC2 gene Author(s) Laššuthová, P. (CZ)
Gregor, Martin (UMG-J) RID, ORCID
Sarnová, Lenka (UMG-J)
Machalová, Eliška (UMG-J)
Sedláček, Radislav (UMG-J) RID
Seeman, P. (CZ)Source Title Journal od Neurogenetics - ISSN 0167-7063
Roč. 26, 3-4 (2012), s. 413-420Number of pages 8 s. Language eng - English Country GB - United Kingdom Keywords exon trapping ; peripheral neuropathy ; SH3TC2 gene ; splice site mutation Subject RIV EB - Genetics ; Molecular Biology R&D Projects GAP303/10/2044 GA ČR - Czech Science Foundation (CSF) Institutional support UMG-J - RVO:68378050 UT WOS 000311679300021 DOI https://doi.org/10.3109/01677063.2012.711398 Annotation Charcot-Marie-Tooth (CMT) neuropathy is the most common inherited neuromuscular disorder. CMT is genetically very heterogeneous. Mutations in the SH3TC2 gene cause Charcot-Marie-Tooth neuropathy type 4C (CMT4C), a demyelinating form with autosomal recessive inheritance. In this study, two novel splice site mutations in the SH3TC2 gene have been studied (c.279G -> A, c.3676-8G -> A). Mutation c.279G -> A was detected on one allele in two unrelated families with CMT4C in combination with a known pathogenic mutation (c.2860 C -> T in one family, c.505T -> C in the other) on the second allele of SH3TC2 gene. Variant c.3676-8G -> A was detected in two patients from unrelated families on one allele of the SH3TC2 gene in combination with c.2860C -> T mutation on the other allele. Several in silico tests were performed and exon trap experiments were undertaken in order to prove the effect of both mutations on proper splicing of SH3TC2. Fragments of SH3TC2 were subcloned into pET01 exon trap vector (Mobitec) and transfected into COS-7 cells. Aberrant splicing was predicted in silico for both mutations, which was confirmed by exon trap analysis. For c.279G -> A mutation, 19 bases from intron 3 are retained in cDNA. The mutation c.3676-8G -> A produces a novel splice acceptor site for exon 17 and complex changes in splicing were observed. We present evidence that mutations c.279G -> A and c.3676-8G -> A in the SH3TC2 gene cause aberrant splicing and are therefore pathogenic and causal for CMT4C. Workplace Institute of Molecular Genetics Contact Nikol Škňouřilová, nikol.sknourilova@img.cas.cz, Tel.: 241 063 217 Year of Publishing 2013
Počet záznamů: 1