A compound heterozygous change found in Peters' anomaly

[摘要] Purpose: To determine whether sequence variations in the congenitalglaucoma gene, CYP1B1, are present in individuals with Peters'anomaly, a developmental eye anomaly frequently associated withglaucoma.Methods: The CYP1B1 coding region was screened in 26 individualswith Peters' anomaly (9 familial and 17 simplex cases) by heteroduplexanalysis using the Transgenomic Wave® nucleic acid fragment analysissystem. Deviations from the wild type pattern were determined bysequencing.Results: Six nucleotide positions varied from the wild type. Four ofthese have previously been observed in clinically normal individuals:-13 in intervening sequence 1 (IVS1), codons 48, 432, and 449. We founda novel sequence variation at -16 in IVS1 in one affected individual. Anovel compound heterozygote pattern was observed at codon 432 in 6 ofour 26 unrelated cases with Peters' anomaly.Conclusions: This is the first report of 2 novel CYP1B1 sequencevariations seen in Peters' anomaly. The -16 IVS1 change is outside thecoding region and likely to be a rare polymorphism. The compoundheterozygous change at codon 432 is within a conserved part of thecoding region and substitutes valine with either leucine or arginine.This change has not been observed in 100 normal controls. Furthermore,we propose how this finding may affect protein function.

[学科分类] 生物化学/生物物理