About: Clinical, in silico, and experimental evidence for pathogenicity of two novel splice site mutations in the SH3TC2 gene

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About: Clinical, in silico, and experimental evidence for pathogenicity of two novel splice site mutations in the SH3TC2 gene Goto Sponge NotDistinct Permalink

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rdf:type	skos:Concept http://linked.opendata.cz/ontology/domain/vavai/Vysledek
Description	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. 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. (en)
Title	Clinical, in silico, and experimental evidence for pathogenicity of two novel splice site mutations in the SH3TC2 gene Clinical, in silico, and experimental evidence for pathogenicity of two novel splice site mutations in the SH3TC2 gene (en)
skos:prefLabel	Clinical, in silico, and experimental evidence for pathogenicity of two novel splice site mutations in the SH3TC2 gene Clinical, in silico, and experimental evidence for pathogenicity of two novel splice site mutations in the SH3TC2 gene (en)
skos:notation	RIV/68378050:_____/12:00386622!RIV13-GA0-68378050
http://linked.open...avai/predkladatel	Ústav molekulární genetiky AV ČR, v. v. i.
http://linked.open...avai/riv/aktivita	I P
http://linked.open...avai/riv/aktivity	I, P(GAP303/10/2044), P(NT11521)
http://linked.open...iv/cisloPeriodika	3-4
http://linked.open...vai/riv/dodaniDat	2013
http://linked.open...aciTvurceVysledku	Sedláček, Radislav Sarnová, Lenka Machalová, Eliška Gregor, Martin
http://linked.open.../riv/druhVysledku	J - Článek v odborném periodiku
http://linked.open...iv/duvernostUdaju	S - Úplné a pravdivé údaje nepodléhající ochraně podle zvláštních právních předpisů
http://linked.open...titaPredkladatele	Ústav molekulární genetiky AV ČR, v. v. i.
http://linked.open...dnocenehoVysledku	127431
http://linked.open...ai/riv/idVysledku	RIV/68378050:_____/12:00386622
http://linked.open...riv/jazykVysledku	eng - angličtina
http://linked.open.../riv/klicovaSlova	exon trapping; peripheral neuropathy; SH3TC2 gene; splice site mutation (en)
http://linked.open.../riv/klicoveSlovo	peripheral neuropathy SH3TC2 gene exon trapping splice site mutation
http://linked.open...odStatuVydavatele	GB - Spojené království Velké Británie a Severního Irska
http://linked.open...ontrolniKodProRIV	[3DA3D94EE68A]
http://linked.open...i/riv/nazevZdroje	Journal od Neurogenetics
http://linked.open...in/vavai/riv/obor	EB
http://linked.open...ichTvurcuVysledku	4 (xsd:int)
http://linked.open...cetTvurcuVysledku	6 (xsd:int)
http://linked.open...vavai/riv/projekt	The Impact of a Liver-Specific Deficiency of Growth Factor Sheddase ADAM10 on Liver Development and Pathology Autosomal recessive demyelinating neuropathy type CMT4C – analysis of the SH3TC2 gene and a clinical study.
http://linked.open...UplatneniVysledku	2012
http://linked.open...v/svazekPeriodika	26
http://linked.open...iv/tvurceVysledku	Sedláček, Radislav Gregor, Martin Laššuthová, P. Machalová, Eliška Sarnová, Lenka Seeman, P.
http://linked.open...ain/vavai/riv/wos	000311679300021
issn	0167-7063
number of pages	8 (xsd:int)
http://bibframe.org/vocab/doi	10.3109/01677063.2012.711398
is http://linked.open...avai/riv/vysledek of	Clinical, in silico, and experimental evidence for pathogenicity of two novel splice site mutations in the SH3TC2 gene

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