RESUMO
This paper presents a mutation as well as a genotype-phenotype analysis of the GJB2 and GJB6 genes in 476 samples from non-syndromic unrelated Argentinean deaf patients (104 familial and 372 sporadic cases). Most of them were of prelingual onset (82 %) and 27 % were cochlear implanted. Variation of sequences was detected in 171 of the 474 patients (36 %). Overall, 43 different sequence variations were identified in GJB2 and GJB6. Four of them are reported for the first time in GJB2: c.233dupG, p.Ala78Ser, p.Val190Asp and p.Cys211Tyr. Mutations in GJB6 were detected in 3 % of patients [nine del(GJB6-D13S1830) and three del(GJB6-D13S1854)]. Of the 43 different variations identified in GJB2, 6 were polymorphisms and of the others, 10 (27 %) were truncating and 27 (73 %) were nontruncating. Patients with two truncating mutations had significantly worse hearing impairment than all other groups. Moderate phenotypes were observed in a group of patients carrying biallelic mutations (23 %). This work shows the high prevalence of GJB2 mutations in the Argentinean population and presents an analysis of moderate phenotypes in our cohort.
Assuntos
Conexinas/genética , Estudos de Associação Genética , Mutação/genética , Alelos , Sequência de Aminoácidos , Audiometria , Conexina 26 , Conexina 30 , Conexinas/química , Análise Mutacional de DNA , Surdez/genética , Deleção de Genes , Humanos , Modelos Moleculares , Dados de Sequência MolecularRESUMO
PURPOSE: We describe a program for the promotion of hearing conservation aimed at the adolescent population. The intent of our program is to (a) detect hearing disorders early, as well as to establish their relation to psychosocial and acoustic factors; (b) devise a follow-up procedure to study relevant variables; (c) evaluate the relation between hearing disorders and genetic factors, and (d) raise the social awareness of the effects of noise and its consequences. METHOD: This program, designed to be carried out over a 7-year period, focuses on participants from technical schools in the city of Cordoba, Argentina. Every student will be examined at age 14-15 years and will be reexamined at age 17-18. There will be a yearly follow-up in those cases in which disorders are detected. RESULTS AND CONCLUSIONS: We discuss the organization and planning of this program, together with its launching in the first of the selected schools. We also describe the findings on the following topics: (a) the hearing data on adolescents (age 14-15 years); (b) their recreational habits, personality traits, and attitudes; and (c) the sound immision characteristics these individuals are exposed to during recreational activities.
Assuntos
Promoção da Saúde , Transtornos da Audição/prevenção & controle , Desenvolvimento de Programas , Adolescente , Feminino , Humanos , Percepção Sonora , Masculino , Música , Avaliação de Programas e Projetos de Saúde , RecreaçãoRESUMO
Recent advances in molecular genetics as well as improved strategies for the prevention and control of non-syndromic hearing loss (NSHL) have contributed to the rising importance of their inherited causes. In this study we report 32 families from Argentine with one (sporadic) or more (familial) individuals affected. All the families were initially screened for mutations in three autosomal nuclear genes and one mutation in mitochondrial DNA. These genes have been found in a great number of familial or sporadic cases of congenital deafness in Caucasians. The mutant allele 35 del G of connexin 26 (GJB2, locus DFNB1 on 13q12) was present in three families. We have investigated the gene encoding otoferlin (OTOF, locus DFNB9 on 2p22-p23) and we found the Q829X mutation in heterocigosity in two families. We have also identified in heterocigosity the 342-kb deletion of connexin 30 (GJB6, locus DFNB1 on 13q12) in one family. On the other hand, we have not found any patient with mitochondrial mutation. Since the screening for other mutations is very expensive, our main goal is to investigate the most frequent mutations in each separate gene in the argentine population and to develop simple and specific tests for each frequent mutations.
Assuntos
Perda Auditiva/genética , Mutação , Adulto , Argentina , Criança , Conexina 26 , Conexinas , Surdez/diagnóstico , Surdez/genética , Feminino , Deleção de Genes , Aconselhamento Genético , Perda Auditiva/diagnóstico , Perda Auditiva Neurossensorial/diagnóstico , Perda Auditiva Neurossensorial/genética , Humanos , Masculino , LinhagemRESUMO
Los últimos avances en genética molecular como así también el desarrollo de estrategias para la prevención y control de las hipoacusias no sindrómicas (HNS), han contribuido al esclarecimiento de las causas hereditarias de las mismas. En este estudio, se seleccionaron 32 familias argentinas con uno (esporádico) o más (familiar) individuos afectados. El análisis genético consistió en la búsqueda de tres genes autosómicos nucleares y uno en el ADN mitocondrial. Estos genes se localizaron en un gran número de casos familiares o esporádicos de sorderas congénitas en Caucásicos. El alelo mutado 35 del G de la conexina 26 (GJB2, locus DFNB1 en 13g12) se presentó en tres familias. Además se investigó el gen que codifica otoferlina (OTOF locus DFNB9 en 2p22-23) encontrándose en dos familias la mutación Q829X en heterocigocidad. También se identificó en una familia portadora heterocigota la deleción de 342 Kb en la conexina 30 (GJB6, locus DFNB1 en 13g12). Por otro lado, no encontramos ningún paciente con la mutación mitocondrial. Debido a que la búsqueda de otras mutaciones es demasiado costosa, nuestro principal objetivo es investigar aquellas mas frecuentes en la población argentina, a fin de desarrollar test simples y específicos para cada una de ellas.
Assuntos
Humanos , Masculino , Feminino , Perda Auditiva/genética , Mutação , Argentina , Surdez/diagnóstico , Surdez/genética , Deleção de Genes , Aconselhamento Genético , Perda Auditiva Neurossensorial/diagnóstico , Perda Auditiva Neurossensorial/genética , Perda Auditiva/diagnóstico , LinhagemRESUMO
Los últimos avances en genética molecular como así también el desarrollo de estrategias para la prevención y control de las hipoacusias no sindrómicas (HNS), han contribuido al esclarecimiento de las causas hereditarias de las mismas. En este estudio, se seleccionaron 32 familias argentinas con uno (esporádico) o más (familiar) individuos afectados. El análisis genético consistió en la búsqueda de tres genes autosómicos nucleares y uno en el ADN mitocondrial. Estos genes se localizaron en un gran número de casos familiares o esporádicos de sorderas congénitas en Caucásicos. El alelo mutado 35 del G de la conexina 26 (GJB2, locus DFNB1 en 13g12) se presentó en tres familias. Además se investigó el gen que codifica otoferlina (OTOF locus DFNB9 en 2p22-23) encontrándose en dos familias la mutación Q829X en heterocigocidad. También se identificó en una familia portadora heterocigota la deleción de 342 Kb en la conexina 30 (GJB6, locus DFNB1 en 13g12). Por otro lado, no encontramos ningún paciente con la mutación mitocondrial. Debido a que la búsqueda de otras mutaciones es demasiado costosa, nuestro principal objetivo es investigar aquellas mas frecuentes en la población argentina, a fin de desarrollar test simples y específicos para cada una de ellas. (AU)
