Genetic heterogeneity of primary open-angle glaucoma in Pakistan

Area of Science:

• Ophthalmology
• Genetics
• Neuroscience

Background:

• Primary open-angle glaucoma (POAG) is a leading cause of irreversible blindness, affecting individuals over 30.
• POAG is a genetically heterogeneous disorder, often inherited in an autosomal dominant pattern.
• Myocilin (MYOC) is the most frequently reported gene associated with POAG.

Purpose of the Study:

• To screen 25 Pakistani POAG families for genetic associations with MYOC and CYP1B1.
• To investigate the genetic basis of POAG in a specific population.

Main Methods:

• Ethical approval and informed consent were obtained from 25 POAG families in Sindh, Pakistan.
• DNA was extracted from blood samples of affected individuals and their family members.
• Genetic screening was performed for MYOC and CYP1B1 genes using established methods.

Main Results:

• A previously reported MYOC variant (c.144G>T) was identified in one family (POAG-06).
• A novel CYP1B1 variant (c.649G>A) was discovered in another family (POAG-02), with pathogenicity confirmed by bioinformatics tools.
• No association with MYOC or CYP1B1 was found in the remaining 23 POAG families.

Conclusions:

• This study reports the first association of a novel CYP1B1 variant in POAG families from southern Pakistan.
• One family was linked to a known MYOC variant.
• The findings underscore the significant genetic heterogeneity of POAG in this population, with most families not linked to MYOC or CYP1B1.