Matsuda Yoshiko, Mineharu Yohei, Kimura Mitsuru, Takagi Yasushi, Kobayashi Hatasu, Hitomi Toshiaki, Harada Kouji H, Uchihashi Yoshito, Funaki Takeshi, Miyamoto Susumu, Koizumi Akio
Department of Neurosurgery, Kyoto University Graduate School of Medicine, Kyoto, Japan; Department of Health and Environmental Sciences, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Department of Neurosurgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.
J Stroke Cerebrovasc Dis. 2017 Aug;26(8):1841-1847. doi: 10.1016/j.jstrokecerebrovasdis.2017.04.019. Epub 2017 May 11.
This study aimed to determine the effectiveness of genetic testing for the p.R4810K variant (rs112735431) of the Mysterin/RNF213 gene, which is associated with moyamoya disease and other intracranial vascular diseases, in the family members of patients with moyamoya disease.
We performed genotyping of the RNF213 p.R4810K polymorphism and magnetic resonance angiography on 59 relatives of 18 index patients with moyamoya disease. Nineteen individuals had follow-up magnetic resonance angiography with a mean follow-up period of 7.2 years.
Six of the 34 individuals with the GA genotype (heterozygotes for p.R4810K) showed intracranial steno-occlusive lesions in the magnetic resonance angiography, whereas none of the 25 individuals with the GG genotype (wild type) showed any abnormalities. Follow-up magnetic resonance angiography revealed de novo lesions in 2 and disease progression in 1 of the 11 individuals with the GA genotype, despite none of the 8 individuals with the GG genotype showing any changes. Accordingly, 8 individuals had steno-occlusive lesions at the last follow-up, and all had the p.R4810K risk variant. The prevalence of steno-occlusive intracranial arterial diseases in family members with the p.R4810K variant was 23.5% (95% confidence interval: 9.27%-37.78%), which was significantly higher than in those without the variant (0%, P = .0160).
Genotyping of the p.R4810K missense variant is useful for identifying individuals with an elevated risk for steno-occlusive intracranial arterial diseases in the family members of patients with moyamoya disease.
本研究旨在确定对Mysterin/RNF213基因的p.R4810K变体（rs112735431）进行基因检测在烟雾病患者家庭成员中的有效性，该变体与烟雾病及其他颅内血管疾病相关。
我们对18例烟雾病索引患者的59名亲属进行了RNF213 p.R4810K多态性基因分型和磁共振血管造影。19名个体接受了随访磁共振血管造影，平均随访期为7.2年。
34例GA基因型（p.R4810K杂合子）个体中有6例在磁共振血管造影中显示颅内狭窄闭塞性病变，而25例GG基因型（野生型）个体均未显示任何异常。随访磁共振血管造影显示，11例GA基因型个体中有2例出现新发病变，1例病情进展，而8例GG基因型个体均未出现任何变化。因此，8例个体在最后一次随访时出现狭窄闭塞性病变，且均具有p.R4810K风险变体。携带p.R4810K变体的家庭成员中颅内动脉狭窄闭塞性疾病的患病率为23.5%（95%置信区间：9.27%-37.78%），显著高于未携带该变体的家庭成员（0%，P = 0.0160）。
对p.R4810K错义变体进行基因分型有助于识别烟雾病患者家庭成员中颅内动脉狭窄闭塞性疾病风险升高的个体。
