Primary Congenital Glaucoma: A Novel Single-Nucleotide Deletion and Varying Phenotypic Expression for the 1546–1555dup Mutation in the GLC3A (CYP1B1) Gene in 2 Families of Different Ethnic Origin

PURPOSETo present new molecular genetic data on primary congenital glaucoma from 2 families, 1 isolated case and 3 familial cases due to mutations in the cytochrome P-450 1B1 (CYP1B1) gene. METHODSAll diagnoses were made by slit-lamp biomicroscopy, gonioscopy, cornea and optic disk measurements, ultrasound-biometry, and automated static threshold perimetry where possible. Mutation screening was performed by direct sequence analysis of DNA extracted from peripheral blood of the patients and their relatives. RESULTSFor the isolated case, a child of 4 years, a homozygous nucleotide deletion within a tetrad of cytosines (nt622–625, 622delC) was found leading to a predicted nonsense codon 93 truncating the protein by 450 amino acids. For the familial cases, the 3 affected members showed a homozygous mutation 1546–1555dupTCATGCCACC for which 9 healthy relatives proved to be heterozygous. The phenotypic expression of these 3 patients varied widely. CONCLUSIONOur results confirm the crucial role of CYP1B1 mutations for congenital glaucoma.