Localization of a gene for otosclerosis to chromosome 15q25-q26

Among white adults otosclerosis is the single most common cause of hearingimpairment. Although the genetics of this disease are controversial, themajority of studies indicate autosomal dominant inheritance with reducedpenetrance. We studied a large multi- generational family in whichotosclerosis has been inherited in an autosomal dominant pattern. Five of16affected persons have surgically confirmed otosclerosis; the remaining ninehave a conductive hearing loss but have not undergone corrective surgery.To locate the disease- causing gene we completed genetic linkage analysisusing short tandem repeat polymorphisms (STRPs) distributed over the entiregenome. Multipoint linkage analysis showed that only one genomic region, onchromosome 15q, generated a lod score >2.0. Additional STRPs were typedin this area, resulting in a lod score of 3.4. STRPs FES (centromeric) andD15S657 (telomeric) flank the 14. 5 cM region that contains an otosclerosisgene.