A second gene for otosclerosis, OTSC2, maps to chromosome 7q34-36

Otosclerosis due to abnormal bone homeostasis of the otic capsule is a freq uent cause of hearing loss in adults. Usually, the hearing loss is conducti ve, resulting from fixation of the stapedial footplate, which prevents norm al ossicular vibration in response to sound. An additional type of sensorin eural hearing loss may be caused by otosclerotic damage to the cochlea. The etiology of the disease is unknown, and both environmental and genetic fac tors have been implicated. Autosomal dominant inheritance with reduced pene trance has been proposed, but large families are extremely rare. To elucida te the pathogenesis of the disease, identification of the responsible genes is essential. In this study, we completed linkage analysis in a Belgian fa mily in which otosclerosis segregates as an autosomal dominant disease. Aft er excluding linkage to a known locus on chromosome 15 (OTSC1), we found li nkage on chromosome 7q, with a multipoint LOD score of 3.54. Analysis of ke y recombinant individuals maps this otosclerosis locus (OTSC2) to a 16-cM i nterval on chromosome 7q34-36 between markers D7S495 and D7S2426.