RESUMEN
The role of myosins in the pathogenesis of hearing loss is well established: five genes encoding unconventional myosins and two genes encoding nonmuscle conventional myosins have so far been described to be essential for normal auditory function and mutations in these genes associated with hearing impairment. To better understand the role of this gene family we performed a mutational screening on two candidate genes, MYO1C and MYO1F, analyzing hundreds of patients, affected by bilateral sensorineural hearing loss and coming from different European countries. This research activity led to the identification of 6 heterozygous missense mutations in MYO1C and additional 5 heterozygous missense mutations in MYO1F. Homology modelling suggests that some of these mutations could have a potential influence on the structure of the ATP binding site and could probably affect the ATPase activity or the actin binding process of both myosins. This study suggests a role of the above mentioned myosin genes in the pathogenesis of hearing loss.
Asunto(s)
Pérdida Auditiva Sensorineural/genética , Miosina Tipo I/genética , Secuencia de Bases , Análisis Mutacional de ADN , Cartilla de ADN/genética , Variación Genética , Heterocigoto , Humanos , Modelos Moleculares , Mutación Missense , Miosina Tipo I/química , Estructura Terciaria de ProteínaRESUMEN
Nonsyndromic sensorineural hearing impairment is inherited in a predominantly autosomal recessive manner in up to 70% of cases. The gene more often involved is GJB2, encoding the gap junction protein Connexin 26. We report here a novel missense mutation in the GJB2 gene found in a Tunisian family. A homozygous change C/G at nucleotide 263 was detected in the 4-year-old girl of this family, affected by congenital moderate hearing loss. This transversion leads to the replacement of a highly conserved alanine with glycine at codon 88 (A88G). The consanguineous parents of the child are healthy carriers of the mutation.
Asunto(s)
Conexinas/genética , Pérdida Auditiva Sensorineural/genética , Patrón de Herencia/genética , Mutación Missense/genética , Preescolar , Conexina 26 , Consanguinidad , Femenino , Pérdida Auditiva Sensorineural/congénito , Pérdida Auditiva Sensorineural/diagnóstico , Humanos , Linaje , TúnezRESUMEN
Pendred syndrome is an autosomal recessive disorder characterized by congenital sensorineural deafness, goitre and defective iodide organification. Congenital and profound hearing loss is the hallmark of the syndrome, while goitre and thyroid dysfunction are highly variable even within the same family. Clinical features are due to altered formation of pendrin, a chloride/iodide transporter protein expressed in the inner ear, thyroid gland and kidney. A novel substitution was found in exon 7 of the pendrin encoding gene (SLC26A4) that leads to a stop codon, S314X. The new variation was found in compound heterozygosity with L445W mutation in a hearing impaired patient with bilateral Mondini's dysplasia and goitre.