Human Genetics

, Volume 123, Issue 3, pp 267–272

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

  • Insaf Bel Hadj Ali
  • Melissa Thys
  • Najeh Beltaief
  • Isabelle Schrauwen
  • Nele Hilgert
  • Kathleen Vanderstraeten
  • Nele Dieltjens
  • Emna Mnif
  • Slah Hachicha
  • Ghazi Besbes
  • Saïda Ben Arab
  • Guy Van Camp
Original Investigation

DOI: 10.1007/s00439-008-0470-3

Cite this article as:
Bel Hadj Ali, I., Thys, M., Beltaief, N. et al. Hum Genet (2008) 123: 267. doi:10.1007/s00439-008-0470-3

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.

Supplementary material

439_2008_470_Fig2_ESM.jpg (211 kb)
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 (86 kb)
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)
439_2008_470_MOESM3_ESM.doc (56 kb)
Supplementary table 1 (DOC 57 kb)
439_2008_470_MOESM4_ESM.doc (44 kb)
Supplementary table 2 (DOC 45 kb)
439_2008_470_MOESM5_ESM.doc (43 kb)
Supplementary table 3 (DOC 43 kb)

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Insaf Bel Hadj Ali
    • 1
  • Melissa Thys
    • 2
  • Najeh Beltaief
    • 1
    • 3
  • Isabelle Schrauwen
    • 2
  • Nele Hilgert
    • 2
  • Kathleen Vanderstraeten
    • 2
  • Nele Dieltjens
    • 2
  • Emna Mnif
    • 4
  • Slah Hachicha
    • 3
  • Ghazi Besbes
    • 3
  • Saïda Ben Arab
    • 1
  • Guy Van Camp
    • 2
  1. 1.Unité d’Epidémiologie Génétique et MoléculaireFaculté de MédecineTunisTunisia
  2. 2.Department of Medical GeneticsUniversity of AntwerpAntwerpBelgium
  3. 3.Service ORL et de Chirurgie Maxillo-facialeHôpital La RabtaTunisTunisia
  4. 4.Service de RadiologieHôpital La Rabta de TunisTunisTunisia