title: [Changes in the connexin 26 (GJB2) gene in Russian patients with hearing disorders: results of long-term molecular diagnostics of hereditary nonsyndromic deafness].
abstract: Search for mutations in the connexin 26 gene (GJB2) is a routine molecular-genetic analysis ofthe hereditary deafness worldwide. However, till now there is no assessment of the diagnostic significance of this analysis for Russian patients, and there are difficulties in interpretation of the results of DNA diagnostics. In the present study, a sample of 705 patients with nonsyndromic autosomal recessive deafness from different regions of Russian Federation was investigated. A portion of deafness like DFNB1 caused by mutations in the GJB2 gene among the sample was 46%. The frequency of deafness of such genetic type was 1:1000, that is, the frequency of isolated autosomal recessive deafness was 1:500 in the population. It was found that each sixteenth individual in Russia is a heterozygous carrier of the mutation in the GJB2gene. Totally, 20 pathological GJB2 alleles were detected; among them, a c.35delG mutation with the allelic frequency 81% prevails. Six most frequent mutations (c.35delG, c.313_326de114, c.-23+1G>A (IVS1+1G>A), c.235delC, c.167delT, and p.Glul20del), which account for 95% of pathological GJB2 alleles, were detected. Mutations previously not described in the GJB2 gene (c.129delG, p.Gly200Arg, and c[Arg127His, Gly160Ser]) were found. An optimal algorithm of molecular investigation of Russian patients which detects up to 100% of mutations in the GJB2 gene was suggested. Data concerning a clinical significance of p.Met34Thr and p.Va137Ile mutations are confirmed in the study. Eight polymorphic substitutions in the GJB2gene which do not have clinical significance (p.Va127Ile, c.*3C>A, p.Va115311e, p.Gly160Ser, c.Arg127His, p.Glull4Gly (c.341A>G), c.-45C>A, and p.Ala149Thr) were also detected.
authors.forename: E A
authors.initials: EA
authors.lastname: Bliznets
authors.forename: V A
authors.initials: VA
authors.lastname: Galkina
authors.forename: G N
authors.initials: GN
authors.lastname: Matiushchenko
authors.forename: A G
authors.initials: AG
authors.lastname: Kisina
authors.forename: T G
authors.initials: TG
authors.lastname: Markova
authors.forename: A V
authors.initials: AV
authors.lastname: Poliakov
mesh_terms: D000072259:Connexin 26; D017630:Connexins / Q000235:genetics*; D005787:Gene Frequency; D005808:Genes, Recessive; D030342:Genetic Diseases, Inborn / Q000175:diagnosis / Q000235:genetics*; D006319:Hearing Loss, Sensorineural / Q000175:diagnosis / Q000235:genetics*; D006801:Humans; D009154:Mutation; D057089:Pathology, Molecular; D012426:Russia
chemical_list: D017630:Connexins; C000607042:GJB2 protein, human; D000072259:Connexin 26