Prevalence of <i>CYP1B1</i> mutations in Australian patients with primary congenial glaucoma

Analysis of <i>CYP1B1</i> in primary congenital glaucoma (PCG) patients from various ethnic populations indicates that allelic heterogeneity is high, and some mutations are population specific. No study has previously reported the rate or spectrum of <i>CYP1B1</i> mutations in Australian PCG patients. The aim of this study is to determine the frequency of <i>CYP1B1</i> mutations in our predominately Caucasian, Australian cohort of PCG cases. Thirty-seven probands were recruited from South-Eastern Australia, along with 100 normal control subjects. Genomic DNA was extracted and the coding regions of <i>CYP1B1</i> analysed by direct sequencing. Sequence analysis identified 10 different <i>CYP1B1</i> disease-causing variants in eight probands (21.6%). Five subjects were compound heterozygotes, two subjects heterozygous and one homozygous for <i>CYP1B1</i> mutations. Three missense mutations are novel (D192Y, G329D, and P400S). None of the novel mutations identified were found in normal controls. One normal control subject was heterozygous for the previously reported <i>CYP1B1</i> R368H mutation. Six previously described probable polymorphisms were also identified. Mutations in <i>CYP1B1</i> account for approximately one in five PCG cases from Australia. Our data also supported the high degree of allelic heterogeneity seen in similar studies from other ethnic populations, thereby underscoring the fact that other PCG-related genes remain to be identified.