Mutation of COL11A2 causes autosomal recessive non-syndromic hearing loss at the DFNB53 locus
- 1Department of Otolaryngology and Head and Neck Surgery, University of Iowa, Iowa City, Iowa, USA
- 2Genetics Research Centre, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran
- 3Department of Medical Genetics, University of Antwerp, Antwerp, Belgium
- Correspondence to: Dr Richard J H Smith Department of Otolaryngology and Head and Neck Surgery, Interdepartmental Genetics Program, The University of Iowa, 200 Hawkins Drive, Iowa City, IA 52242, USA;
- Received 10 March 2005
- Accepted 4 July 2005
- Revised 30 June 2005
- Published Online First 20 July 2005
Background: Allele variants of COL11A2, encoding collagen type XI α2, cause autosomal dominant non-syndromic hearing loss (ARNSHL) at the DFNA13 locus (MIM 601868) and various syndromes that include a deafness phenotype.
Objective: To describe a genome-wide scan carried out on a consanguineous Iranian family segregating ARNSHL.
Results: Genotyping data identified a novel locus for ARNSHL on chromosome 6p21.3, which was designated DFNB53. Homozygosity for the P621T mutation of COL11A2 was present in all deaf persons in this family; this same variation was absent in 269 Iranian controls. Sequence comparison of collagen type XI α1 and α2 peptides across species shows that the replaced proline is an evolutionarily conserved amino acid.
Conclusions: The P621T mutation of COL11A2 affects the Y position of the canonical -Gly-X-Y- repeat in collagens. It lies near the amino-terminus of the triple helical region and causes ARNSHL. This finding suggests that mutation type and location are critical determinants in defining the phenotype of COL11A2 associated diseases.
- ARNSHL, autosomal recessive non-syndromic hearing loss
- OSMED, otospondylomegaepiphyseal dysplasia
- PCR–RFLP, polymerase chain reaction–restriction fragment length polymorphism
Competing interests: none declared