title: 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.
authors.affiliation: Unité d'Epidémiologie Génétique et Moléculaire, Faculté de Médecine, 1007, Tunis, Tunisia.
authors.forename: Insaf
authors.initials: I
authors.lastname: Bel Hadj Ali
authors.forename: Melissa
authors.initials: M
authors.lastname: Thys
authors.forename: Najeh
authors.initials: N
authors.lastname: Beltaief
authors.forename: Isabelle
authors.initials: I
authors.lastname: Schrauwen
authors.forename: Nele
authors.initials: N
authors.lastname: Hilgert
authors.forename: Kathleen
authors.initials: K
authors.lastname: Vanderstraeten
authors.forename: Nele
authors.initials: N
authors.lastname: Dieltjens
authors.forename: Emna
authors.initials: E
authors.lastname: Mnif
authors.forename: Slah
authors.initials: S
authors.lastname: Hachicha
authors.forename: Ghazi
authors.initials: G
authors.lastname: Besbes
authors.forename: Saïda
authors.initials: S
authors.lastname: Ben Arab
authors.forename: Guy
authors.initials: G
authors.lastname: Van Camp
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002503:Centromere / Q000235:genetics*; D002874:Chromosome Mapping; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics*; D005260:Female; D005799:Genes, Dominant; D008040:Genetic Linkage / Q000235:genetics*; D005819:Genetic Markers; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008126:Lod Score; D008297:Male; D008875:Middle Aged; D010040:Otosclerosis / Q000453:epidemiology / Q000235:genetics*; D010375:Pedigree; D011110:Polymorphism, Genetic; D020080:Tandem Repeat Sequences
chemical_list: D005819:Genetic Markers