Chromosomal mapping and phenotypic characterization of hereditary otosclerosis linked to the OTSC4 locus

To perform chromosomal mapping and clinical analysis of hereditary otosclerosis linked to the fourth locus for otosclerosis (OTSC4) in an Israeli family.

Pedigree study.

A genetics of hearing loss research laboratory, a clinical genetics laboratory, a center for speech and hearing, and an otolaryngology department at a university and medical centers in Israel.

An Israeli family of which 24 members were ascertained and a pedigree was constructed; 12 members had otosclerosis.

Confirmation of otosclerosis by surgery (3 subjects) and by audiologic evaluation, medical history, and family history (9 subjects), and whole-genome scanning to identify the chromosomal region of the mutant locus.

Chromosomal location of the otosclerosis locus.

Linkage to the 16q21-23.2 interval was identified and confirmed with a logarithm of odds (LOD) score of 3.97 at theta = 0. The new locus for otosclerosis was designated OTSC4. The OTSC4 interval of 9 to 10 megabase includes several genes involved in the immune system and bone homeostasis that may be good candidates for genes otosclerosis.

The elucidation of the OTSC4 gene may disclose the etiology of the disorder, and the functional and structural analysis of the protein may open new options for diagnosis, treatment, and prevention of otosclerosis.