RESUMO
OBJECTIVE: To determine the incidence of GJB2 and GJB3 mutations and of two deletions upstream of the GJB6 gene in infants of the Campania region of southern Italy. DESIGN: DNA samples from non-syndromic hearing-impaired infants enrolled in a neonatal screening programme for sensorineural hearing loss were analysed by PCR and by direct sequencing. The audiological features of infants with biallelic GJB2 mutations were also examined to identify genotype-phenotype correlations. STUDY SAMPLE: Molecular analyses were carried out in 129 affected and five unaffected infants. RESULTS: A genetic etiology of hearing loss was identified in 28% of infants, including several at environmental risk of hearing loss. Neither GJB6 nor GJB3 (a gene not previously investigated in the Campania population) mutations were found. CONCLUSIONS: This study confirms the importance of universal neonatal hearing screening. The identification of a genetic cause in infants at environmental risk indicates that such infants should be included when investigating etiology. We confirm that also in our geographical area, c.35delG homozygotes tend to have severe symmetrical hearing loss, whereas hearing impairment is milder in compound heterozygotes.
Assuntos
Conexinas/genética , Perda Auditiva Neurossensorial/genética , Conexina 26 , Conexina 30 , Análise Mutacional de DNA , Estudos de Associação Genética , Perda Auditiva Neurossensorial/epidemiologia , Humanos , Incidência , Lactente , Itália/epidemiologia , Programas de Rastreamento , Deleção de SequênciaRESUMO
The aim of this study was to screen 349 patients affected by sensorineural hearing loss (SNHL), mostly from the Campania region (southern Italy), for GJB2 gene mutations and for two deletions of the GJB6 gene (del GJB6 -D13S1830 and del GJB6 -D13S1854). We identified pathogenetic GJB2 mutations in 51 cases (15% of patients). No GJB6 mutation was found. We also examined the audiologic features of the patients for whom we had an etiologic diagnosis, in order to identify correlations between the severity of hearing loss and the type of mutation.
Assuntos
Conexinas/genética , Testes Genéticos , Perda Auditiva Neurossensorial/genética , Programas de Rastreamento/métodos , Mutação , Estimulação Acústica , Adolescente , Adulto , Audiometria , Percepção Auditiva , Criança , Pré-Escolar , Conexina 26 , Conexina 30 , Predisposição Genética para Doença , Perda Auditiva Neurossensorial/epidemiologia , Perda Auditiva Neurossensorial/fisiopatologia , Heterozigoto , Homozigoto , Humanos , Itália/epidemiologia , Pessoa de Meia-Idade , Fenótipo , Fatores de Risco , Índice de Gravidade de Doença , Adulto JovemRESUMO
The GJB2 gene located on chromosome 13q12 and encoding the connexin 26 (Cx26) protein, a transmembrane protein involved in cell-cell attachment of almost all tissues, including the skin, causes autosomal recessive and sometimes dominant nonsyndromic sensorineural hearing loss. GJB2 mutations have also been identified in syndromic disorders exhibiting hearing loss associated with skin problems. Recently, a new mutation, p.G130V in the GJB2 gene has been reported as causative for Vohwinkel syndrome. In this case the p.G130V mutation was found in two patients (son and father) with palmoplantar keratoderma. The father also showed also skin constrictions of the 2nd and 3rd toes of the right foot. Here, we report on another family with palmoplantar keratoderma associated with a dominant form of hearing loss confirming the genotype-phenotype correlation between the mutation p.G130V and the skin abnormalities observed in syndromic disorders with hearing loss as described by [Snoeckx et al. (2005) Hum Mutat 26:60-65].
