Genetic heterogeneity in autosomal dominant otosclerosis: Exclusion of linkage to four known loci in an Italian family

Aim. Clinical otosclerosis is one of the most common cause of hearing impairment among white adults with a prevalence of 0.3-0.4%. Epidemiological studies indicate the involvement of genetic and environmental factors, and there are also suggestions of a viral influence. To date six autosomal loci for otosclerosis have been identified in six families belonging to different geographical areas: OTSC1 (15q25-q26), OTSC2 (7q34-q36), OTSC3 (6p21.3-p22.3), OTSC4 (16q 21-23.2), OTSC5 (3q22-q24) and OTSC7 (6q13-16.1). Methods. We report the study of one Italian family affected with otosclerosis; we studied history and/or clinical signs in 5 generations members. It was possible to perform a complete clinical and instrumental examination in 16 subjects belonging to the last wo generations. Results. We identified 8 patients affected by otosclerosis, while the other 8 family members were free of disease on clinical grounds. These findings proved to be unlinked to four reported loci (OTSC1, OTSC2, OTSC3 and OTSC5) thus confirming the presence of extensive genetic heterogeneity. Conclusion. The results obtained suggest the existence of more additional loci responsible for the disease or an interaction between genes and environmental factors.