RESUMO
Ninety genes have been identified to date that are involved in non-syndromic hearing loss, and more than 300 different forms of syndromic hearing impairment have been described. Mutations in SOX10, one of the genes contributing to syndromic hearing loss, induce a large range of phenotypes, including several subtypes of Waardenburg syndrome and Kallmann syndrome with deafness. In addition, rare mutations have been identified in patients with isolated signs of these diseases. We used the recent characterization of temporal bone imaging aspects in patients with SOX10 mutations to identify possible patients with isolated hearing loss due to SOX10 mutation. We selected 21 patients with isolated deafness and temporal bone morphological defects for mutational screening. We identified two SOX10 mutations and found that both resulted in a non-functional protein in vitro. Re-evaluation of the two affected patients showed that both had previously undiagnosed olfactory defects. Diagnosis of anosmia or hyposmia in young children is challenging, and particularly in the absence of magnetic resonance imaging (MRI), SOX10 mutations can mimic non-syndromic hearing impairment. MRI should complete temporal bones computed tomographic scan in the management of congenital deafness as it can detect brain anomalies, cochlear nerve defects, and olfactory bulb malformation in addition to inner ear malformations.
Assuntos
Perda Auditiva/genética , Mutação , Fatores de Transcrição SOXE/genética , Osso Temporal/patologia , Adolescente , Adulto , Idoso , Sequência de Aminoácidos , Sequência de Bases , Criança , Análise Mutacional de DNA , Diagnóstico Diferencial , Orelha Interna/anormalidades , Feminino , Estudos de Associação Genética , Perda Auditiva Neurossensorial/genética , Humanos , Imageamento por Ressonância Magnética , Masculino , Dados de Sequência Molecular , Fenótipo , Fatores de Transcrição SOXE/química , Síndrome de Waardenburg/genéticaRESUMO
Hearing impairment is characterized by great genetic heterogeneity. We report the identification, by whole exome sequencing, of two different nonsense mutations (c.1558C>T; p.Gln520 and c.2773C>T; p.Arg925) in the otogelin-like gene (OTOGL), in a child affected by mild to moderate isolated deafness. Parental genotypes allowed us to conclude that these mutations are present in the compound heterozygous state in the patient. In addition, our clinical data establish that the tectorial membrane and/or the outer hair cells are defective in this form of deafness.