title: High frequency of SH3TC2 mutations in Czech HMSN I patients.
abstract: Charcot-Marie-Tooth (CMT) neuropathy type 4C (CMT4C) is an autosomal recessive (AR), demyelinating neuropathy with early spine deformities caused by mutations in the SH3TC2 gene. To determine the spectrum of SH3TC2 mutations in the Czech population, the entire coding region of SH3TC2 was sequenced in 60 unrelated Czech patients. The prevalent mutation was shown to be the p.Arg954Stop. Therefore, 412 additional patients referred for CMT testing were tested for the presence of p.Arg954Stop only. Of 60 patients in whom the SH3TC2 gene was sequenced, at least one mutation was detected in 13 (21.7%) patients and biallelic pathogenic mutations were detected in 7 (11.6%) patients. Of the 412 patients tested for p.Arg954Stop, the mutation was found in 8 patients (1.94%), 6 were homozygous and 2 were heterozygous. The second causative mutation was detected by sequencing in one of the patients but not in the other. Nine novel sequence variants were detected. Their pathogenicity was further tested in silico and in control samples. Mutations in the SH3TC2 gene are a frequent cause of demyelinating hereditary neuropathy among Czech patients. In total, at least one mutation was found in 21 unrelated patients. CMT4C seems to be the most frequent type of AR CMT and one of the most frequent of all CMT types. Mutation p.Arg954Stop is highly prevalent in the Czech population. Patients with demyelinating neuropathy along with non-dominant mode of inheritance and negative for CMT1A/hereditary neuropathy with liability to pressure palsy should be tested for the presence of the p.Arg954Stop mutation or other mutations in the SH3TC2 gene.
authors.affiliation: DNA Laboratory, Department of Child Neurology, 2nd Medical School, University Hospital Motol, Prague, Czech Republic. petra.lassuthova@gmail.com
authors.forename: P
authors.initials: P
authors.lastname: Laššuthová
authors.forename: R
authors.initials: R
authors.lastname: Mazanec
authors.forename: P
authors.initials: P
authors.lastname: Vondráček
authors.forename: D
authors.initials: D
authors.lastname: Sišková
authors.forename: J
authors.initials: J
authors.lastname: Haberlová
authors.forename: J
authors.initials: J
authors.lastname: Sabová
authors.forename: P
authors.initials: P
authors.lastname: Seeman
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics*; D002648:Child; D018153:Czech Republic; D005091:Exons; D005260:Female; D005838:Genotype; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008875:Middle Aged; D009154:Mutation; D020125:Mutation, Missense; D010375:Pedigree; D010641:Phenotype; D011506:Proteins / Q000235:genetics*; D055815:Young Adult
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; C488620:SH3TC2 protein, human