A Nonsense MITF Mutation Associated with Autosomal Dominant Hearing Loss and Intra-Family Clinical Heterogeneity

Abstract

involving hearing loss includes Branchio-Oto-Renal syndrome, ARTICLE INFO ABSTRACTObjectives: Hearing loss is the most common sensory disorder in humans. Approximately 60% of cases of congenital hearing loss have a genetic aetiology. Consequently, the genetic study would significantly improve the diagnostic performance of these hearing impairments avoiding unnecessary tests and helping to establish the evolution, prognosis and treatment of the disease. These studies are of great relevance in cases of syndromic hearing loss.Methods: Using an own designed panel of next generation sequencing (NGS), we studied the case of a two year old boy, with a congenital bilateral NSHL detected through neonatal hearing screening. The patient did not present any other associated pathology. As the hearing loss was profound and bilateral, it was decided to place a cochlear implant in both ears when he was one year old. Results:The analysis revealed the presence of the heterozygous mutation c.1066C>T, p. (Arg356*), in the MITF (NM_198159.2) gene which was confirmed by Sanger sequencing. The segregation study of the mutation in the MITF gene was performed in the family and only the father showed the same mutation with a different phenotype. Conclusion:We describe the clinical spectrum in a family with MITF mutation. They are a clear example of incomplete intrafamilial penetrance and variable expressivity already reported in other cases with MITF mutations.