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.
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Acknowledgments
We thank the family members for their cooperation. This work was supported by the European Commission FP6 Integrated Project EUROHEAR LSHG-CT-2004-512063, NIH grant R01DC05218 and the Ministère de l’Enseignement Supérieur, de la Recherche Scientifique et de la Technologie, Tunisia. MT holds a predoctoral research position with the Institute for the Promotion of Innovation through Science and Technology in Flanders (IWT-Vlaanderen). IS and NH hold a predoctoral research position with the ‘Fonds voor Wetenschappelijk Onderzoek Vlaanderen’ (FWO).
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439_2008_470_Fig2_ESM.jpg
Supplementary fig. 1 A: Normal CT-scan of the labyrinthine of an unaffected control person. B: CT scan showing hypodensity of the labyrinthine capsule (arrow) with pericochlear topography (retrofenestral otosclerosis) of an affected family member (LK5, left ear). (JPG 210 kb)
439_2008_470_Fig3_ESM.gif
Supplementary fig. 2 Segmental duplications in the 9p13.1-9q21.11 region. The positions of the markers are given in Mb on the physical map (NCBI, Build 36 version 2). We identified duplicons a and b. The other duplicons shown in the figure are based on the findings of Paulis et al. (2004). (GIF 86 kb)
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Bel Hadj Ali, I., Thys, M., Beltaief, N. et al. A new locus for otosclerosis, OTSC8, maps to the pericentromeric region of chromosome 9. Hum Genet 123, 267–272 (2008). https://doi.org/10.1007/s00439-008-0470-3
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DOI: https://doi.org/10.1007/s00439-008-0470-3