Linkage of otosclerosis to a third locus (OTSC3) on human chromosome 6p21.3-22.3

Abstract

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.

Genetic variants in RELN are associated with otosclerosis in a non‐European population from Tunisia

“…Linkage analysis studies on large families in which autosomal dominant otosclerosis segregates have been used to identify eight monogenic loci (OTSC1 (Tomek et al, 1998), OTSC2 (Van Den Bogaert et al, 2001), OTSC3 (Chen et al, 2002), OTSC4 (Brownstein et al, 2006), OTSC5 (Van Den Bogaert et al, 2004), OTSC7 (Thys et al, 2007b) and OTSC8 (Bel Hadj Ali et al, 2008)) located on chromosomes 15q25-q26, 7q34-36, 6p21.3-22.3, 16q21-23.2, 3q22-24, 6q13-16.1 and 9p13.1-9q21.11 respectively. The OTSC6 locus has not been published, although it has been reserved with the Human Genome Organisation Nomenclature Committee (http://www.genenames.org/).…”

A seventh locus for otosclerosis, OTSC7, maps to chromosome 6q13–16.1

“…To date, five autosomal dominant otosclerosis loci have been reported: OTSC1 on chromosome 15q25 -26, 4 OTSC2 on chromosome 7q34 -36, 5 OTSC3 on chromosome 6p21 -22, 6 OTSC4 on chromosome 16q21 -23.2, 7 and OTSC5 on chromosome 3q22 -24. 8 In addition, a sixth locus, OTSC6, has been reported to the Human Genome Organisation nomenclature committee but details describing this locus have not been published.…”

Les surdités héréditaires : génétique moléculaire

“…Le nombre croissant de familles identifiées dans lesquelles la surdité se révèle tardivement, indique que la contribution des facteurs génétiques a été sous-estimée. En particulier, ces facteurs seraient importants pour l'otospongiose [13].…”