Of mice and men: tyrosinase modification of congenital glaucoma in mice but not in humans.
OBJECTIVE
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.
Bidinost
Carla
C
Health Research and Education Center, Washington State University Spokane, Spokane, Washington 99210-1495, USA.
Hernandez
Natalie
N
Edward
Deepak P
DP
Al-Rajhi
Ali
A
Lewis
Richard Alan
RA
Lupski
James R
JR
Stockton
David W
DW
Bejjani
Bassem A
BA
D000293:Adolescent; D000328:Adult; D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D002648:Child; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D065633:Cytochrome P-450 CYP1B1; D004252:DNA Mutational Analysis; D005901:Glaucoma / Q000151:congenital* / Q000235:genetics*; D006801:Humans; D008126:Lod Score; D051379:Mice; D014442:Monophenol Monooxygenase / Q000235:genetics*; D009154:Mutation; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012529:Saudi Arabia
D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; C585498:Cyp1b1 protein, mouse; D065633:Cytochrome P-450 CYP1B1; D014442:Monophenol Monooxygenase