HMSN/CMT 1X: Spectrum and frequency of mutations in the connexin 32 gene (GJB1)

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Genetika. 2008 Oct;44(10):1385-91.

Spectrum and frequency of mutations in the connexin 32 gene (GJB1) in

hereditary and sensory neuropathy type 1X patients from Bashkortostan

[article in Russian]

[No authors listed]

Hereditary motor and sensory neuropathy type 1X (HMSN 1X) is the

second most frequent form of demyelinating polyneuropathies and is

caused by mutations in the gene for connexin 32 protein (Cx32, GJB1).

The contribution of HMSN 1X to the structure of HMSN in the Republic

of Bashkortostan was determined.

The GJB1 mutations were detected in 18 out of 131 unrelated patients,

which constituted 13.7%. The four missense mutations identified were

represented by: Pro87Ala (c.259C>G) with the frequency of 10%;

Arg22Gln (c.65G>A) (2.98%); Arg15Gln (c.44G>A); and Thr86Ile

(c.257C<T) (0.8%). The latter mutation was never described before.

The frequent mutation Pro87Ala was tested for linkage disequilibrium

with the alleles of five polymorphic microsatellite DNA loci

associated with the GJB1. It was demonstrated that 10 out of 13

chromosomes carrying the mutation mentioned had common DXS8111-DXS983-

DXS8107-DXS8052 haplotype.

This finding suggested the distribution of this mutation on the

territory of the Republic of Bashkortostan as a result of the founder

effect. The mutational spectrum of GJB1 and mutation frequencies

observed in the HMSN 1X patients examined were characterized by

ethnic heterogeneity. This finding will provide development of most

optimal algorithm of the HMSN DNA diagnostics in the region.