TY - JOUR
T1 - Of mice and men
T2 - Tyrosinase modification of congenital glaucoma in mice but not in humans
AU - Bidinost, Carla
AU - Hernandez, Natalie
AU - Edward, Deepak P.
AU - Al-Rajhi, Ali
AU - Lewis, Richard Alan
AU - Lupski, James R.
AU - Stockton, David W.
AU - Bejjani, Bassem A.
PY - 2006/4
Y1 - 2006/4
N2 - PURPOSE. Primary congenital glaucoma (PCG) is an autosomal recessive ocular trait caused by mutations in the gene for cytochrome P4501B1 (CYP1B1). Although PCG is often considered to be fully penetrant, the disease shows 50% penetrance in some Saudi Arabian families. The familial segregation of the nonpenetrance suggests a genetic modifier. Recently, tyrosinase (Tyr) deficiency was found to worsen the drainage structure/ocular dysgenesis phenotype of Cyp1b1 -/- mice, suggesting that Tyr is a modifier of the phenotype. In the current study, tyrosinase (TYR) was investigated in human PCG. METHODS. A genome-wide screen, a single nucleotide polymorphism (SNP) analysis in the TYR chromosomal region 11q13-q21, and sequencing of the TYR gene was performed with individuals from Saudi Arabian families with multiple, clinically confirmed, molecularly proven, nonpenetrant members. RESULTS. The study outcome did not support TYR as a modifier of the PCG phenotype in this population. The sequencing data showed no TYR mutations in the nonpenetrant family members and no difference in polymorphism frequencies between nonpenetrant or fully penetrant families. CONCLUSIONS. TYR is not a modifier of the CYP1B1-associated PCG phenotype in the Saudi Arabian population.
AB - PURPOSE. Primary congenital glaucoma (PCG) is an autosomal recessive ocular trait caused by mutations in the gene for cytochrome P4501B1 (CYP1B1). Although PCG is often considered to be fully penetrant, the disease shows 50% penetrance in some Saudi Arabian families. The familial segregation of the nonpenetrance suggests a genetic modifier. Recently, tyrosinase (Tyr) deficiency was found to worsen the drainage structure/ocular dysgenesis phenotype of Cyp1b1 -/- mice, suggesting that Tyr is a modifier of the phenotype. In the current study, tyrosinase (TYR) was investigated in human PCG. METHODS. A genome-wide screen, a single nucleotide polymorphism (SNP) analysis in the TYR chromosomal region 11q13-q21, and sequencing of the TYR gene was performed with individuals from Saudi Arabian families with multiple, clinically confirmed, molecularly proven, nonpenetrant members. RESULTS. The study outcome did not support TYR as a modifier of the PCG phenotype in this population. The sequencing data showed no TYR mutations in the nonpenetrant family members and no difference in polymorphism frequencies between nonpenetrant or fully penetrant families. CONCLUSIONS. TYR is not a modifier of the CYP1B1-associated PCG phenotype in the Saudi Arabian population.
UR - http://www.scopus.com/inward/record.url?scp=33645976785&partnerID=8YFLogxK
U2 - 10.1167/iovs.05-0763
DO - 10.1167/iovs.05-0763
M3 - Article
C2 - 16565383
AN - SCOPUS:33645976785
VL - 47
SP - 1486
EP - 1490
JO - Investigative Ophthalmology and Visual Science
JF - Investigative Ophthalmology and Visual Science
SN - 0146-0404
IS - 4
ER -