Founder Mutation Effect Seen ByCERKLGene Mutation Causing Retinal Dystrophy in North Indian Population

Abstract

PurposeThis paper describes the clinical features, genotype phenotype correlation ofCERKLgene mutation, one of the most common genetic mutations of Inherited Retinal Dystrophy (IRD) patients seen in our cohort in North India.Materials and MethodsPatients clinically diagnosed with an IRD were included in the study. Patients underwent ultra widefield (UWF) fundus photographs, fundus autofluorescence (FAF), optical coherence tomography (OCT). A pedigree charting was done. Genetic testing by next generation sequencing (NGS) was done, clinical exome was analyzed.ResultsWe report ophthalmic and genetic findings of seven patients withCERKLgene mutation of the thirty five patients that chose to undergo genetic sequencing (amongst our cohort of sixty two patients with IRD). The age ranged from 17 to 45 (median 25) years. Vision ranged from LogMAR 0.18 to 1.8. OCT showed central macular thickness (CMT) ranging from 103 to 268 microns. Majority patients’ fundus exhibited macular pigmentary changes with atrophy, paucipigmentary or limited peripheral retinal pigmentary changes; mild optic disc pallor, and minimal vascular attenuation. Stippled hypo autofluorescence at the macula was the most common finding, with minimal hypoautoflorescence in the retinal periphery.. The genetic sequencing of all patients showed the same mutation, a 2 base pair deletion in exon 7 of theCERKLgene (chr2:g.181548785_181548786del). Coincidentally, all patients withCERKLgene mutation were found to be from a single ethnic community suggesting a founder mutation effect.ConclusionsMutation in theCERKLgene results are among the most common causes of IRD in North India. Affected patients showed a definitive early macular involvement. This study reports the presence of a founder mutation effect in theCERKLgene in a large ethnic community in North India.