Linkage of otosclerosis to a third locus (OTSC3) on human chromosome 6p21.3-22.3.
Clinical otosclerosis (OMIM 166800/605727) has a prevalence of 0.2-1% among white adults, making it the single most common cause of hearing impairment in this group. It is caused by abnormal bone homeostasis of the otic capsule with the consequent development of sclerotic foci that invade the stapedio-vestibular joint (oval window) interfering with free motion of the stapes. Impaired ossicular chain mobility results in a conductive hearing loss. We identified the first locus for otosclerosis (OTSC1) on chromosome 15 in 1998 and reported a second locus (OTSC2) on chromosome 7 last year. Here we present results of a genome wide linkage study on a large Cypriot family segregating otosclerosis. Results of this study exclude linkage to OTSC1 and OTSC2 and identify a third locus, OTSC3, on chromosome 6p. The defined OTSC3 interval covers the HLA region, consistent with reported associations between HLA-A/HLA-B antigens and otosclerosis.
Molecular Otolaryngology Research Laboratories, Department of Otolaryngology-Head and Neck Surgery, University of Iowa Hospitals and Clinics, Iowa City, IA, USA.
W
W
Chen
C A
CA
Campbell
G E
GE
Green
K
K
Van Den Bogaert
C
C
Komodikis
L S
LS
Manolidis
E
E
Aconomou
Y
Y
Kyamides
K
K
Christodoulou
C
C
Faghel
C M
CM
Giguére
R L
RL
Alford
S
S
Manolidis
G
G
Van Camp
R J H
RJ
Smith
D002874:Chromosome Mapping / Q000379:methods; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage / Q000235:genetics*; D005819:Genetic Markers / Q000235:genetics*; D005820:Genetic Testing; D006801:Humans; D008126:Lod Score; D008297:Male; D010040:Otosclerosis / Q000235:genetics*; D010375:Pedigree
D005819:Genetic Markers