title: High prevalence of the IVS 1 + 1 G to A/GJB2 mutation among Czech hearing impaired patients with monoallelic mutation in the coding region of GJB2.
abstract: Biallelic pathogenic GJB2 gene mutations cause pre-lingual genetic hearing loss in up to 50% of individuals with bilateral sensorineural hearing loss worldwide. Sequencing of the entire GJB2 gene-coding region in Czech patients with pre-lingual bilateral hearing loss revealed that 10.3% of Czech patients carry only one monoallelic pathogenic mutation in the coding region of the GJB2 gene, which is significantly more than the population frequency of 3.4%. The 309-kb GJB6 deletion, frequent in Spain and France, is very rare in the Czech population. In order to evaluate the impact of the IVS1 + 1 G to A splice site mutation in the non-coding part of the GJB2 gene among Czech patients, we tested all available patients with pre-lingual hearing loss with only one monoallelic mutation in the coding part of GJB2. By sequencing of the exon 1 region of the GJB2 gene and HphI restriction analysis in 20 Czech patients we identified nine patients carrying IVS1 + 1 G to A. Testing for this mutation explained deafness in 45% of Czech GJB2 monoallelic patients. This mutation represents now 4% of GJB2 pathogenic mutations in Czech patients and is the third most common GJB2 mutation found in our cohort of 242 unrelated Czech patients with prelingual hearing loss. A similar frequency may also be expected in other Central European or Slavic populations.
authors.affiliation: Department of Child Neurology, DNA Laboratory, Charles University Prague, 2nd School of Medicine, Prague, Czech Republic. pseeman@yahoo.com
authors.forename: P
authors.initials: P
authors.lastname: Seeman
authors.forename: I
authors.initials: I
authors.lastname: Sakmaryová
mesh_terms: D000483:Alleles; D015331:Cohort Studies; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics*; D018153:Czech Republic; D004252:DNA Mutational Analysis; D005820:Genetic Testing; D006312:Hearing Loss, Bilateral / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D009154:Mutation; D022821:RNA Splice Sites / Q000235:genetics*; D015183:Restriction Mapping
chemical_list: D017630:Connexins; C000607042:GJB2 protein, human; D022821:RNA Splice Sites; D000072259:Connexin 26