Arg4810Lys Mutation inRNF213among Eastern Indian Non-MMD Ischemic Stroke Patients: A Genotype-Phenotype Correlation

Abstract

Introduction: RNF213 mutations have been reported mostly in Moyamoya Disease (MMD) with varying frequencies across different ethnicities. However, its prevalence in non-MMD adult-onset Ischemic Stroke is still not well explored. Aims & Objectives: This present study thus aims to screen the most common RNF213 variant (Arg4810Lys, among East Asians) in the Eastern Indian non-MMD Ischemic Stroke patients and correlate it with long-term progression and prognosis of the patients. The subjects were analysed for this variant using PCR-RFLP and confirmed using Sanger sequencing method. Result & Conclusion: We have identified Arg4810Lys variant among eleven young-onset familial Ischemic Stroke patients in heterozygous manner. A positive correlation of the variant with positive family history (P = 0.001), earlier age-at-onset (P = 0.002), history of recurrent stroke (P = 0.015) was observed. However, the carriers showed better cognitive performances in memory (P = 0.042) and executive function (P = 0.004). Therefore, we can conclude that Arg4810Lys/RNF213 - a pathogenic variant for young-onset familial Ischemic Stroke with higher incidence of recurrent events unlike in MMD cases, have no additional impact on cognition among Eastern Indians.