A new locus for otosclerosis, OTSC8, maps to the pericentromeric region of chromosome 9

Abstract

Otosclerosis is a common disorder of the otic capsule resulting in hearing impairment in 0.3-0.4% of the Caucasian population. The aetiology of the disease remains unclear. In most cases, otosclerosis can be considered as a complex disease. In some cases, the disease is inherited as an autosomal dominant trait, sometimes with reduced penetrance. To date, seven autosomal dominant loci have been reported, but none of the disease-causing genes has been identified. In this study, we present the results of a genome-wide linkage analysis in a large Tunisian family segregating autosomal dominant otosclerosis. Linkage analysis localised the responsible gene to chromosome 9p13.1-9q21.11 with a maximal LOD score of 4.13, and this locus was named OTSC8. Using newly generated short tandem repeat polymorphism markers, we mapped this new otosclerosis locus to a 34.16 Mb interval between the markers D9S970 and D9S1799. This region comprises the pericentromeric region on both arms of chromosome 9, a highly complex region containing many duplicated sequences.

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/).…”

Cochlear otosclerosis

“…Even though the eight loci have been reported so far in patients with otosclerosis, there is still uncertainty about the ratio of cochlear otosclerosis in these groups [4–10]. In addition, the responsible disease related genes in those loci remain unclear.…”

Genetic Association and Altered Gene Expression of Osteoprotegerin in Otosclerosis Patients

“…Usually, OTSC transmits in an autosomal dominant fashion with reduced penetrance. In recent years, many efforts have been made to elucidate the molecular genetics of OTSC in multicase families, resulting in the identification of ten monogenic loci (Tomek et al, 1998;Van Den Bogaert et al, 2001;Chen et al, 2002;Van Den Bogaert et al, 2004;Brownstein et al, 2006;Thys et al, 2007b;Bel Hadj Ali et al, 2008;Weegerink et al, 2011). Despite meticulous searches through these regions, the disease causing genes have not been identified so far.…”