Mutation of COL11A2 causes autosomal recessive non-syndromic hearing loss at the DFNB53 locus.
BACKGROUND
Allele variants of COL11A2, encoding collagen type XI alpha2, 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 alpha1 and alpha2 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.
Chen
W
W
Kahrizi
K
K
Meyer
N C
NC
Riazalhosseini
Y
Y
Van Camp
G
G
Najmabadi
H
H
Smith
R J H
RJ
D000595:Amino Acid Sequence; D024161:Collagen Type XI / Q000235:genetics*; D005260:Female; D005808:Genes, Recessive; D008040:Genetic Linkage; D014644:Genetic Variation; D006319:Hearing Loss, Sensorineural / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D007492:Iran; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype
C499319:COL11A2 protein, human; D024161:Collagen Type XI