A compound heterozygous change found in Peters' anomaly.

PURPOSE To determine whether sequence variations in the congenital glaucoma gene, CYP1B1, are present in individuals with Peters' anomaly, a developmental eye anomaly frequently associated with glaucoma. METHODS The CYP1B1 coding region was screened in 26 individuals with Peters' anomaly (9 familial and 17 simplex cases) by heteroduplex analysis using the Transgenomic Wave nucleic acid fragment analysis system. Deviations from the wild type pattern were determined by sequencing. RESULTS Six nucleotide positions varied from the wild type. Four of these have previously been observed in clinically normal individuals: -13 in intervening sequence 1 (IVS1), codons 48, 432, and 449. We found a novel sequence variation at -16 in IVS1 in one affected individual. A novel compound heterozygote pattern was observed at codon 432 in 6 of our 26 unrelated cases with Peters' anomaly. CONCLUSIONS This is the first report of 2 novel CYP1B1 sequence variations seen in Peters' anomaly. The -16 IVS1 change is outside the coding region and likely to be a rare polymorphism. The compound heterozygous change at codon 432 is within a conserved part of the coding 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.