Study of Clinical Characteristics and Screening of Exon 2 of PDE6A gene in Non-Syndromic Familial Retinitis Pigmentosa cases in Pakistan

Abstract

Retinitis Pigmentosa (RP) is a hereditary condition in which the retina of the eye, specifically the photoreceptor layer, degenerates over time. Over 2.5 million people worldwide are thought to be affected with RP. The global prevalence is approximately 1:4000. Eye exam of RP patients indicate weakened retinal vessels, an irregular fundus with an accumulation of bone spicules, a waxy pallor of the optic disc, macular degeneration, and arterial attenuation. The onset age and degree of RP's severity varies, ranging from early childhood to late adulthood and barely perceptible tunnel vision to central vision impairment respectively. RP can be inherited in one of three ways: X-linked RP, autosomal recessive RP, or autosomal dominant RP. Both syndromic and non-syndromic types of RP are possible. According to reports, the most prevalent form of retinal dystrophies in the Pakistani population is autosomal recessive RP. The Al-Shifa Trust Eye Hospital in Rawalpindi, Pakistan, and the Bio Ethical Review Committee of Quaid-i-Azam University in Islamabad, Pakistan, provided clearance for this study. Sampling was done from August 2022 till February 2023. 20 families with positive family history were collected. An ophthalmologist made the RP diagnosis for all the participating families. Participants were questioned about their family history of illness, a pedigree was drawn, and medical data were gathered. After receiving written authorization, blood samples were taken from both affected and unaffected members. For genetic analysis, genomic DNA was collected. In order to amplify exon 2 of the PDE6A gene for mutational investigation, primers were created. The amplified products were purified and sent for Sanger's sequencing after the amplification of a chosen exon. In this study 20% cases show autosomal dominant pattern of inheritance, 80% cases indicate autosomal recessive mode of inheritance, and no other inheritance pattern was observed. All the RP patients had progressive RP. The ratio of male RP patients was greater than the female RP patients i.e., 57.14% males and 42.86% females. In this study, 20 cases were reported in which 80% (16 families) have non-syndromic RP while 20% cases (4 families) have syndromic RP. The average age of diagnosis of RP patients in this study was 22.64 years and the median was 20 years. 95% families reported in this study has cousin marriages. The findings of this study demonstrated that consanguinity is a factor causing high incidence of illnesses that are recessively inherited, including RP. Genetic counseling was offered to all participating families as a result.