A new locus for otosclerosis, OTSC8, maps to the pericentromeric region of chromosome 9.
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.
Bel Hadj Ali
Insaf
I
Unité d'Epidémiologie Génétique et Moléculaire, Faculté de Médecine, 1007, Tunis, Tunisia.
Thys
Melissa
M
Beltaief
Najeh
N
Schrauwen
Isabelle
I
Hilgert
Nele
N
Vanderstraeten
Kathleen
K
Dieltjens
Nele
N
Mnif
Emna
E
Hachicha
Slah
S
Besbes
Ghazi
G
Ben Arab
Saïda
S
Van Camp
Guy
G
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
D005819:Genetic Markers