CMT 4C: High frequency of SH3TC2 mutations in Czech HMSN I patients

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High frequency of SH3TC2 mutations in Czech HMSN I patients.

High frequency of SH3TC2 mutations in Czech HMSN I patients.

Petra L, Radim M, Petr V, Dana S, Jana H, Jana S, Pavel S.

2nd Medical School and University Hospital Motol, DNA Laboratory, Dept of Child

Neurology, Prague, Czech Republic 2nd Medical School and University Hospital

Motol, Dept of Neurology, Prague, Czech Republic The University Hospital Brno,

Clinic of Pediatric Neurology, Brno, Czech Republic Thomayer University

Hospital, Department of Child Neurology,Prague, Czech Republic University

Hospital Motol, DNA Laboratory, Dept of Child Neurology, Prague, Czech Republic.

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.

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 patients (21.7%) and biallelic pathogenic

mutations were detected in seven (11.6%) patients.

Of the 412 patients tested for p.Arg954Stop, the mutation was found in eight

patients (1.94%), six were homozygous and two 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. At least one mutation was found in total in 21 unrelated patients.

CMT4C seems to be the most frequent type of AR CMT type and one of the most

frequent of all CMT types. Mutation p.Arg954Stop is highly prevalent in the

Czech population. Patients with demyelinating neuropathy with non-dominant mode

of inheritance and negative for CMT1A/HNPP should be tested for the presence of

the p.Arg954Stop mutation or other mutations in the SH3TC2 gene.