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


METHODS
Pedigree study.


METHODS
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.


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


METHODS
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.


METHODS
Chromosomal location of the otosclerosis locus.


RESULTS
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.


CONCLUSIONS
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.
Brownstein
Zippora
Z
Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
Goldfarb
Abraham
A
Levi
Haya
H
Frydman
Moshe
M
Avraham
Karen B
KB
D000328:Adult; D000368:Aged; D001299:Audiometry; D002874:Chromosome Mapping; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D006314:Hearing Loss, Conductive / Q000235:genetics*; D006801:Humans; D007557:Israel; D008126:Lod Score; D008297:Male; D008875:Middle Aged; D010040:Otosclerosis / Q000235:genetics*; D010375:Pedigree; D019683:Penetrance; D010641:Phenotype