RESUMEN
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.
Asunto(s)
Conexinas/genética , Pérdida Auditiva Sensorineural/genética , Conexina 26 , Conexina 30 , Análisis Mutacional de ADN , Estudios de Asociación Genética , Pérdida Auditiva Sensorineural/epidemiología , Humanos , Incidencia , Lactante , Italia/epidemiología , Tamizaje Masivo , Eliminación de SecuenciaRESUMEN
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.
Asunto(s)
Conexinas/genética , Pruebas Genéticas , Pérdida Auditiva Sensorineural/genética , Tamizaje Masivo/métodos , Mutación , Estimulación Acústica , Adolescente , Adulto , Audiometría , Percepción Auditiva , Niño , Preescolar , Conexina 26 , Conexina 30 , Predisposición Genética a la Enfermedad , Pérdida Auditiva Sensorineural/epidemiología , Pérdida Auditiva Sensorineural/fisiopatología , Heterocigoto , Homocigoto , Humanos , Italia/epidemiología , Persona de Mediana Edad , Fenotipo , Factores de Riesgo , Índice de Severidad de la Enfermedad , Adulto JovenRESUMEN
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].
Asunto(s)
Conexinas/genética , Pérdida Auditiva Sensorineural/complicaciones , Pérdida Auditiva Sensorineural/genética , Queratodermia Palmoplantar/complicaciones , Queratodermia Palmoplantar/genética , Mutación Puntual , Audiometría de Tonos Puros , Preescolar , Conexina 26 , Femenino , Genes Dominantes , Genotipo , Pérdida Auditiva Sensorineural/fisiopatología , Humanos , Queratodermia Palmoplantar/patología , Masculino , Linaje , Fenotipo , SíndromeRESUMEN
The etiology of otosclerosis is unknown. The etiopathogenesis of otosclerosis seems similar to that occurring in Paget's disease of bone, for which mutations or polymorphisms in several genes have been identified. Among these, TNFRSF11B gene encoding the osteoprotegerin is produced at high levels in the normal inner ear and at low level in active otosclerotic stapes footplates. The aim of this work was to verify the presence of a correlation between the rs2073618 (N3K) polymorphism in the TNFRSF11B gene and otosclerosis. Mutational screening in the TNFRSF11B gene was performed by direct sequencing. SNPs analysis was performed by PCR and by specific restriction enzyme assay with HpaI. The significance of the association was analyzed by statistical specific software. No causative mutation has been identified but the data suggested a strong correlation between the rs2073618 (N3K) polymorphism and otosclerosis. This correlation, however, has been excluded in a case-control study. This study excluded the association between the N3K polymorphism and otosclerosis in Campania region population.
RESUMEN
We ascertained a large Italian family with an autosomal dominant form of non-syndromic sensorineural hearing loss with vestibular involvement. A genome-wide scan found linkage to locus DFNA11. Sequencing of the MYO7A gene in the linked region identified a new missense mutation resulting in an Ala230Val change in the motor domain of the myosin VIIA. Myosin VIIA has already been implicated in several forms of deafness, but this is the third mutation causing a dominant form of deafness, located in the myosin VIIA motor domain in a region never involved in hearing loss until now. A modelled protein structure of myosin VII motor domain provides evidence for a significant functional effect of this missense mutation.