CMT X: Six New Gap Junction Beta 1 Gene Mutations and Their Phenotypic Expressio

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Genet Test Mol Biomarkers. 2009 Dec 29.

Six New Gap Junction Beta 1 Gene Mutations and Their Phenotypic Expression in

Czech Patients with Charcot-Marie-Tooth Disease.

Brožková D, Mazanec R, Haberlová J, Sakmaryová I, Subrt I, Seeman P.

1 DNA Laboratory, Department of Child Neurology, University 2nd Medical

School and University Hospital Motol , Prague, Czech Republic .

X-linked Charcot-Marie-Tooth (CMTX) disease is a hereditary motor and sensory

neuropathy caused by mutations in the gap junction beta 1 gene (GJB1 codes for

connexin 32).

In this study we report six novel mutations p.Met1Arg, p.Leu9Phe, p.Ser17Tyr,

p.Val63Phe, p.Val170Ile, and p.Leu212Phe in GJB1 and their phenotypic

expression. These mutations affect both intracellular and extracellular parts of

the GJB1 protein.

The screened patients had previously excluded the duplication/deletion on

17p11.2 and the male-to-male transfer in the pedigree.

Except p.Val170Ile, all reported mutations segregated with the CMT phenotype in

the families and caused CMTX1 neuropathy. Mutations were not found in 200

control DNA samples.

Additionally, we performed in silico analysis of the novel mutations with the

program PANTHER. The PANTHER scored five mutations, all but p.Val170Ile, as

likely deleterious and supported the pathogenicity of the found mutations. These

results provided evidence that these five mutations are causative for CMTX1.