在日本患者中，RNF213 p.R4810K 变异的缺失可能表明存在严重形式的儿科烟雾病。
Absence of the RNF213 p.R4810K variant may indicate a severe form of pediatric moyamoya disease in Japanese patients.
机构信息
1Department of Neurosurgery, Tokyo Medical and Dental University, Tokyo.
2Department of Neurosurgery, Tokyo Women's Medical University Institute for Integrated Medical Sciences, Tokyo; and.
出版信息
J Neurosurg Pediatr. 2021 Oct 8;29(1):48-56. doi: 10.3171/2021.7.PEDS21250. Print 2022 Jan 1.
OBJECTIVE
The authors' objective was to investigate the influence of the RNF213 p.R4810K variant on the clinical presentation and outcomes of Japanese pediatric patients with moyamoya disease.
METHODS
A total of 129 Japanese patients with pediatric-onset moyamoya disease (onset age ≤ 15 years) who visited the authors' department from 2012 to 2020 participated in this study. After RNF213 p.R4810K genotyping of each patient was performed, the relationship between genotype and clinical presentation or outcomes, including onset age, initial presentation, surgical outcomes, and subsequent cerebrovascular events, was evaluated. Patients without the p.R4810K variant were tested for RNF213 variants other than p.R4810K. The authors especially focused on the results of patients who presented with moyamoya disease at younger than 1 year of age (infantile onset).
RESULTS
Compared with the patients with heterozygous variants, patients without the p.R4810K variant were younger at onset (7.1 ± 3.7 vs 4.4 ± 0.9 years), and all 4 patients with infantile onset lacked the p.R4810K variant. A greater proportion of patients without the p.R4810K variant presented with infarction than patients with the heterozygous variant (24.0% vs 7.6%) and a decreased proportion presented with transient ischemic attack (36.0% vs 71.7%). No significant correlation was observed between p.R4810K genotype and clinical outcomes, including surgical outcomes and subsequent cerebrovascular events; however, a decreased proportion of patients without the p.R4810K variant had good surgical outcomes compared with that of patients with the heterozygous variant (76.5% vs 92.2%). Among the 25 patients without the p.R4810K variant, 8 rare variants other than p.R4810K were identified. Three of 4 patients with infantile onset had RNF213 variants other than p.R4810K, which had a more severe functional effect on this gene than p.R4810K.
CONCLUSIONS
Absence of the RNF213 p.R4810K variant may be a novel biomarker for identification of a severe form of pediatric moyamoya disease.
目的
作者旨在探讨 RNF213 p.R4810K 变异对日本儿科烟雾病患者临床表型和结局的影响。
方法
本研究纳入了 2012 年至 2020 年期间作者所在科室就诊的 129 例发病年龄≤15 岁的日本儿科烟雾病患者。对每位患者进行 RNF213 p.R4810K 基因型检测后，评估基因型与临床表型或结局（包括发病年龄、首发症状、手术结局和随后的脑血管事件）的关系。未携带 p.R4810K 变异的患者检测了除 p.R4810K 以外的 RNF213 变异。作者特别关注发病年龄小于 1 岁（婴儿期发病）的患者的结果。
结果
与携带杂合变异的患者相比，不携带 p.R4810K 变异的患者发病年龄更小（7.1±3.7 岁 vs. 4.4±0.9 岁），且所有 4 例婴儿期发病的患者均不携带 p.R4810K 变异。不携带 p.R4810K 变异的患者中，梗死的比例高于携带杂合变异的患者（24.0% vs. 7.6%），而短暂性脑缺血发作的比例低于携带杂合变异的患者（36.0% vs. 71.7%）。p.R4810K 基因型与手术结局和随后的脑血管事件等临床结局之间未见显著相关性；然而，不携带 p.R4810K 变异的患者中，手术结局良好的比例高于携带杂合变异的患者（76.5% vs. 92.2%）。在不携带 p.R4810K 变异的 25 例患者中，发现了 8 种除 p.R4810K 以外的罕见变异。4 例婴儿期发病的患者中，有 3 例存在除 p.R4810K 以外的 RNF213 变异，这些变异对该基因的功能影响比 p.R4810K 更严重。
结论
不携带 RNF213 p.R4810K 变异可能是识别儿科烟雾病严重形式的一种新的生物标志物。
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