RESUMO
OBJECTIVE: To explore the spectrum of Cytochrome P450 1B1 gene variants and genotype-phenotype correlations in families affected with primary congenital glaucoma. METHODS: The cross-sectional study was performed at the Department of Biotechnology, Lahore College for Women University, Lahore, and the School of Biological Sciences, University of the Punjab, Lahore, Pakistan, from February 2015 to October 2016. Six consanguineous families having individuals affected with primary congenital glaucoma were recruited from different hospitals of the city. Sanger sequencing of coding exon of Cytochrome P450 1B1 gene was performed in order to identify the variants segregating with the disorder. RESULTS: All six families had multiple individuals affected with primary congenital glaucoma. Five out of six families (83%, 5/6) showed CYP1B1 mutations upon Sanger sequencing.All eighteen patients of five families with homozygous Cytochrome P450 1B1 gene variants had different degrees of severity of the phenotypes. Clinical evaluation of the affected members revealed congenital glaucoma with a severe phenotype of corneal oedema, photophobia and corneal scarring. The onset of the phenotype was reported to be congenital but the clinical diagnosis was delayed in four cases since medical help was not sought by the families till much later. CONCLUSIONS: The different degrees of severe phenotypes even in individuals with the same Cytochrome P450 1B1 gene mutation suggested the involvement of modifiers in reducing or increasing the disease severity.
