Mutation of COL11A2 causes autosomal recessive non-syndromic hearing loss at the DFNB53 locus -: art. no. e61

Background: Allele variants of COL11A2, encoding collagen type XI alpha 2, 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 alpha 1 and alpha 2 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.