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.
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.
Authors: Stuart W Tompson; Carlos A Bacino; Nicole P Safina; Michael B Bober; Virginia K Proud; Tara Funari; Michael F Wangler; Lisette Nevarez; Leena Ala-Kokko; William R Wilcox; David R Eyre; Deborah Krakow; Daniel H Cohn Journal: Am J Hum Genet Date: 2010-10-28 Impact factor: 11.025
Authors: Maryam Beheshtian; Mojgan Babanejad; Hela Azaiez; Niloofar Bazazzadegan; Diana Kolbe; Christina Sloan-Heggen; Sanaz Arzhangi; Kevin Booth; Marzieh Mohseni; Kathy Frees; Mohammad Hossein Azizi; Ahmad Daneshi; Mohammad Farhadi; Kimia Kahrizi; Richard Jh Smith; Hossein Najmabadi Journal: Arch Iran Med Date: 2016-10-01 Impact factor: 1.354
Authors: Stuart W Tompson; Eissa Ali Faqeih; Leena Ala-Kokko; Jacqueline T Hecht; Rika Miki; Tara Funari; Vincent A Funari; Lisette Nevarez; Deborah Krakow; Daniel H Cohn Journal: Am J Med Genet A Date: 2012-01-13 Impact factor: 2.802
Authors: Margit Schraders; Laura Ruiz-Palmero; Ersan Kalay; Jaap Oostrik; Francisco J del Castillo; Orhan Sezgin; Andy J Beynon; Tim M Strom; Ronald J E Pennings; Celia Zazo Seco; Anne M M Oonk; Henricus P M Kunst; María Domínguez-Ruiz; Ana M García-Arumi; Miguel del Campo; Manuela Villamar; Lies H Hoefsloot; Felipe Moreno; Ronald J C Admiraal; Ignacio del Castillo; Hannie Kremer Journal: Am J Hum Genet Date: 2012-11-02 Impact factor: 11.025