Abstract:
To find the CYP1B1 mutations associated with primary congenital glaucoma (PCG) in Pakistani consanguineous pedigrees. After getting informed consent, 02 consanguineous families belonging to different ethnic groups were enrolled. Detailed medical history was recorded and pedigrees were drawn. The standard ophthalmological examination was done to characterize the phenotype. Genomic DNA was extracted from 10 mL whole blood and coding exons and exon intron boundaries of CYP1B1 gene were directly sequenced. Bioinformatics tools were used to model the mutant protein and predict the effect of novel variants on protein structure and function. Sequencing analysis revealed a novel variant, a non-sense mutation p.L13* was segregating with PCG in two affected of family GLIU-01. It resulted due to a homozygous transition and transversion on two adjacent bases, c.37C>T and c.38T>A, causing premature stop codon at the same position thus truncating the protein, p.(L13*). The variant resulted into the smallest CYP1B1 peptide, just 13 amino acids long, lacking all the functional units of CYP1B1 protein. Both affected were homozygous, whereas parents were carriers and variants segregated with the PCG phenotype. This type of variant has not been described from Pakistan previously. Identification of novel CYP1B1 variant reasserts the genetic heterogeneity of Pakistani PCG patients. The patients with Missense mutations show severe phenotypic presentations and poor vision after surgical interventions as compare to patients with null variants. This may help to better understand the role of CYP1B1 mutations in the development of PCG and its course of pathogenicity.
Page(s):
100-100
DOI:
DOI not available
Published:
Journal: Abstract Book on Global Science Technology and Management Conference, Volume: 0, Issue: 0, Year: 2023