RESUMO
Mutations in the GJB2 gene are responsible for more than half of all cases of recessive non-syndromic deafness. This article presents a mutation analysis of the GJB2, GJB6, OTOF and MTRNR1 genes in 252 patients with sensorineural non-syndromic hearing loss. Thirty-one different mutations were identified in GJB2 and GJB6 in 86 of the 252 (34%) patients. We describe for the first time two new mutations in GJB2: the missense mutation c.29 T>C (p.Leu10Pro) in the N terminal domain and c.326 G>T (p.Gly109Val) in the intracytoplasmic domain of connexin 26. This work shows the high prevalence of GJB2 mutations in the Argentinean population, with frequencies that are comparable to those of the Mediterranean area. Most important, it adds two novel GJB2 mutations to be taken into consideration in the genetic diagnosis of non-syndromic sensorineural hearing loss.
Assuntos
Conexinas/genética , Perda Auditiva/genética , Mutação , Polimorfismo de Nucleotídeo Único , Substituição de Aminoácidos , Argentina , Conexina 26 , Primers do DNA , Mutação da Fase de Leitura , Genes Recessivos , Variação Genética , Humanos , Íntrons , Reação em Cadeia da Polimerase/métodos , Polimorfismo Genético , Deleção de SequênciaRESUMO
CONCLUSION: There were no apparent differences in speech performance after cochlear implantation between patients with biallelic GJB2 and/or GJB6 mutations and those with deafness of unknown aetiology. These data have important implications for the selection of prognostic indicators of the outcome of cochlear implantation. OBJECTIVE: To compare performance after cochlear implantation in children with mutations in GJB2 (connexin 26) and/or GJB6 (connexin 30) and children with deafness of unknown aetiology. SUBJECTS AND METHODS: Genetic analysis and speech performance evaluation was determined in 24 patients with (n=11) and without (n=13) biallelic GJB2 and/or GJB6 mutations who underwent cochlear implantation. Speech perception skills were measured 12 and 24 months after surgery. Each patient was classified in accordance with the speech perception category (SPC). RESULTS: Overall, the two groups showed similar significant improvement in speech perception after implantation.
Assuntos
Implante Coclear , Conexinas/genética , Surdez/congênito , Percepção da Fala , Audiometria da Fala , Estudos de Casos e Controles , Pré-Escolar , Conexina 26 , Conexina 30 , Análise Mutacional de DNA , Surdez/cirurgia , Feminino , Humanos , Lactente , Masculino , MutaçãoRESUMO
Genetically caused congenital deafness is a common trait affecting 1 in 2000 children and it is predominantly inherited in an autosomal recessive fashion. Several mutations in the GJB2 gene and a deletion of 342 kb in GJB6 (delGJB6-D13S1830) have been identified worldwide in patients with hearing impairment. The aim of this study was to determine the prevalence of these mutations in Argentina. Non-syndromic 46 probands (17 familial and 29 sporadic cases) were genetically evaluated. Mutations in GJB2 and/or delGJB6-D13S1830 were found in 19 patients, accounting for 41.3% of the sample. Of the 46 patients investigated in this study, 12 (26.1%) were diagnosed to carry sequence variations in both alleles; all but one, were considered causative for hearing impairment in those patients. In 7 out of 46 patients (15.2%) only one mutant allele was detected. Of their 38 chromosomes, 71% resulted with mutations in the GJB2 gene and 11% in GJB6. The most frequent mutation in GJB2 (24%) was c.35delG (11% homozygous and 13% heterozygous and compound heterozygous). In addition, 11 sequence variations different from c.35delG, were identified in the coding region of the GJB2 gene: T8M, V27I, M34T, E47X, R75W, W77R, I82M, L90P, E129K, V153I, M163V. The delGJB6-D13S1830 mutation was found in 4 patients (9%), 3 of them associated with GJB2 mutations, resulting in compound heterozygous for the DFNB1 locus. The present study demonstrates that mutations in the GJB2 gene and the delGJB6-D13S1830 are prevalent in the Argentinean population.