Analysis of a common PDE6A Mutation (p.Arg102Ser) in Retinitis Pigmentosa Cases from Pakistani Population

Abstract

Retinitis pigmentosa (RP) is a genetic disorder characterized by the progressive degeneration of retina of eye mainly the photoreceptor layer. Approximately more than 2.5 million peoples are affected from RP across the globe. Its estimated prevalence is about 1:4000 worldwide. Eye examination have revealed, weakening of retinal vessels, abnormal fundus with bone spicules accumulation, waxy pallor of optic disc, macular degeneration, and arterial attenuation. The age of onset of RP, varies from early childhood to late adulthood. The severity of RP also varies from mild unnoticeable loss of visual field to tunnel vision and impaired central vision. The mode of inheritance of RP can be autosomal dominant RP, autosomal recessive RP or X-linked RP. RP may exist in syndromic and non-syndromic forms. It is reported that, autosomal recessive RP is the most common form of retinal dystrophies in Pakistani population. This study was performed to analyze a common mutation of PDE6A gene i.e. c.304C>A, p.R102S, in twenty four consanguineous RP families recruited from different regions of Pakistan. Ethical approval was obtained from the Bio-ethical review committee, Faculty of Biological Sciences, Quaid-i-Azam University Islamabad, Pakistan and Al-Shifa Trust Eye Hospital Rawalpindi, Pakistan. All the enrolled families were diagnosed with RP by ophthalmologist. Participating members were interviewed for family history of disease, pedigree drawing, and clinical records were collected. Blood samples were collected from affected and unaffected members after written consent. The genomic DNA was extracted for genetic analysis. Primers were designed to amplify hotspot exon 1 of PDE6A gene for mutational analysis. After the amplification of selected exon, the amplified products were purified and sent for Sanger’s sequencing. Sequencing data analysis did not identified previously reported missense variant c.304C>A causing (p.Arg102Ser) in exon 1 of PDE6A gene in any of the enrolled families. However, other previously reported and novel variants were identified in exon 1 of PDE6A in enrolled RP families. For families in which no disease-causing variant was identified, screening of remaining exons of PDE6A and other reported genes be performed to identify molecular genetic defect. Results of this study also showed that consanguinity contributes to high incidence of recessively inherited disorders including RP in our population. For this reason, genetic counselling was provided to all participating families.