Digenic inheritance of mutations in EPHA2 and SLC26A4 in Pendred syndrome.

摘要: Enlarged vestibular aqueduct (EVA) is one of the most commonly identified inner ear malformations in hearing loss patients including Pendred syndrome. While biallelic mutations SLC26A4 gene, encoding pendrin, causes non-syndromic with EVA or syndrome, a considerable number appear to carry mono-allelic mutation. This suggests faulty pendrin regulatory machinery results loss. Here we identify EPHA2 as another causative gene syndrome SLC26A4. EphA2 forms protein complex controlling localization, which disrupted some pathogenic pendrin. Moreover, point leading amino acid substitution are from bearing mutation Ephrin-B2 binds triggering internalization inducing autophosphorylation weakly. The mutants attenuate ephrin-B2- but not ephrin-A1-induced Our uncover an unexpected role Eph/ephrin system epithelial function.