RESUMO
Clinical and genetic characteristics are presented of 2 patients from a Dutch Usher syndrome type III family who have a new homozygous USH3 gene mutation: 149-152delCAGG + insTGTCCAAT. One individual (IV:1) is profoundly hearing impaired and has normal vestibular function and retinitis punctata albescens (RPA). The other individual is also profoundly hearing impaired, but has well-developed speech, vestibular areflexia, and retinitis pigmentosa sine pigmento (RPSP). These findings suggest that Usher syndrome type III can be clinically misdiagnosed as either Usher type I or II; that Usher syndrome patients who are profoundly hearing impaired and have normal vestibular function should be tested for USH3 mutations; and that RPA and RPSP can occur as fundoscopic manifestations of pigmentary retinopathy in Usher syndrome.
Assuntos
Perda Auditiva Neurossensorial/genética , Proteínas de Membrana/genética , Retinose Pigmentar/genética , Adulto , Limiar Auditivo/fisiologia , Criança , Diagnóstico Diferencial , Eletronistagmografia , Feminino , Genótipo , Perda Auditiva Neurossensorial/diagnóstico , Humanos , Masculino , Linhagem , Fenótipo , Mutação Puntual/genética , Reflexo Anormal/fisiologia , Reflexo Vestíbulo-Ocular/fisiologia , Retinose Pigmentar/diagnóstico , Síndrome , Vestíbulo do Labirinto/fisiologiaRESUMO
Usher syndrome type III is an autosomal recessive disorder characterized by progressive sensorineural hearing loss, vestibular dysfunction, and retinitis pigmentosa. The disease gene was localized to 3q25 and recently was identified by positional cloning. In the present study, we have revised the structure of the USH3 gene, including a new translation start site, 5' untranslated region, and a transcript encoding a 232-amino acid protein. The mature form of the protein is predicted to contain three transmembrane domains and 204 residues. We have found four new disease-causing mutations, including one that appears to be relatively common in the Ashkenazi Jewish population. We have also identified mouse (chromosome 3) and rat (chromosome 2) orthologues, as well as two human paralogues on chromosomes 4 and 10.