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Arg4810Lys Mutation in RNF213 among Eastern Indian Non-MMD Ischemic Stroke Patients: A Genotype-Phenotype Correlation

Sadhukan, D.; Mitra, P.; Mishra, S.; Roy, A.; Podder, G.; Ray, B. K.; Biswas, A.; Hui, S. P.; Banerjee, T. K.; Biswas, A.

2023-06-05 genetic and genomic medicine
10.1101/2023.05.30.23290718 medRxiv
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IntroductionRNF213 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 & ObjectivesThis 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 & ConclusionWe 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.

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