RNF213 p.Arg4810Lys Heterozygosity in Moyamoya Disease Indicates Early Onset and Bilateral Cerebrovascular Events

AbstractThe relationship betweenRNF213 c.14429G  >  A (p.Arg4810Lys) heterozygous variants and clinical manifestation in patients with Moyamoya disease (MMD) remains unclear. We performed a retrospective cohort analysis to clarify the genotype–phenotype correlation of thisRNF213 hotspot variant in MMD patients, especially between wild-type (GG) and heterozygous (GA) genotypes. Clinical and genetic data were obtained from patients diagnosed with MMD in our institutions between October 2011 and November 2020. Clinical data included age, sex, neurological status at diagnosis, medical history, smoking history, alcohol intake, and family history. Of the 225 enrolled patients, 160 (71.1%) were symptomatic, 3 (1.3%) had the homozygous variant, and 149 (66.2%) had the heterozygous variant (GA). Analysis of all enrolled patients showed that the GA group was prone to present bilateral symptoms (p = 0.008) and progressive status (Suzuki grade ≥ 4;p = 0.017). Analysis limited to symptomatic patients revealed that the GA group had bilateral symptoms (p = 0.017), younger age at onset (p = 0.043), and, in particular, a higher proportion of onset before 25 years of age (p = 0.021). Multivariate logistic regression analysis of overall patients revealed that earlier age at diagnosis (p <  0.001, OR 0.936, 95% CI 0.914–0.959) and GA group (p = 0.017, OR 3.326, 95%CI 1.237–8.941) were significantly associated with bilateral symptoms. MMD patient...
Source: Translational Stroke Research - Category: Neurology Source Type: research