• DOI:10.1136/jmg.2004.018671
• Corpus ID: 6898266

A fifth locus for otosclerosis, OTSC5, maps to chromosome 3q22–24

@article{VanDenBogaert2004AFL,
  title={A fifth locus for otosclerosis, OTSC5, maps to chromosome 3q22–24},
  author={Kris Van Den Bogaert and Els De Leenheer and W Chen and Y Lee and Peter J. N{\"u}rnberg and R J E Pennings and Kathleen Vanderstraeten and Melissa Thys and Cor W.R.J. Cremers and R J Smith and Guy Van Camp},
  journal={Journal of Medical Genetics},
  year={2004},
  volume={41},
  pages={450 - 453}
}

• K. Van Den Bogaert, E. De Leenheer, +8 authors G. Van Camp
• Published 1 June 2004
• Medicine
• Journal of Medical Genetics

Otosclerosis is caused by abnormal bone homeostasis of the otic capsule leading to bony fixation of the stapedial footplate in the oval window. Because the transmission of sound waves from outer to inner ear is disturbed by this fixation, the disease is characterised by conductive hearing impairment.1 In some cases, an additional sensorineural component develops across all frequencies, leading to mixed hearing impairment.2,3 The conductive component of the hearing impairment can be restored by stapes replacing microsurgery; however, the sensorineural component cannot surgically be corrected.4

Otosclerosis has a prevalence of 0.3–0.4% in the Caucasian population.5 The etiology of the disease is unknown, but epidemiological studies indicate the involvement of genetic as well as environmental factors. However, large families segregating otosclerosis are very rare, whereas there are frequent sporadic cases and smaller families with only a few affected members. Based on these findings, otosclerosis can be considered a genetically complex disease, caused by an interaction of genes and environmental factors, but with rare monogenic forms.

To date, three autosomal dominant otosclerosis loci have been reported: OTSC1 on chromosome 15q25–26,6 OTSC2 on chromosome 7q34–36,7 and OTSC3 on chromosome 6p21–22.8 In addition, a fourth locus, OTSC4 , has been reserved by the Human Genome Organisation nomenclature committee, but this has not been published. None of the corresponding genes have been cloned. In this study, we identified a large Dutch family segregating an autosomal dominant otosclerosis. After exclusion of the known loci, a genome-wide screen and linkage analysis in this family revealed the existence of a fifth otosclerosis locus, OTSC5 , localised on chromosome 3q22–24.

### Clinical diagnosis

The family was identified via the Department of Otorhinolaryngology of the University Medical Center St.-Radboud Nijmegen (The Netherlands) (fig 1). Pure-tone audiometry was performed in all persons with air conduction at …