<i>RNF213</i>基因突变所致烟雾病一家系病例临床分析并文献复习

doi:10.11817/j.issn.1673-9248.2023.05.012

目的

了解家族烟雾病基因突变的特点。

方法

对北京市大兴区人民医院2014年至2016年间发现的一家系烟雾病患者及其直系亲属进行基因检测，抽取先证者及其亲属外周静脉血，通过DNA外显子测序的方法进行基因测序，并进行头颅MRI+MRA检查。

结果

基因测序结果表明先证者及其母亲、哥哥、表哥、姥姥、姨妈、表妹、舅舅、表侄为RNF213基因60号外显子的杂合变体，发生c.14399A＞G（p.N4800S）突变，先证者的父亲、女儿、侄子未发现该基因位点突变，影像学检查发现先证者及其哥哥、表哥患有烟雾病。

结论

RNF213基因可能是烟雾病的罕见致病基因。

关键词: 烟雾病, RNF213, 遗传学, 脑卒中, 遗传变异

Objective

To understand the characteristics of gene mutation of familial moyamoya disease.

Methods

A family of moyamoya disease and their immediate relatives were subjected to gene testing between 2014 and 2016 at People's of Hospital of Bejing Daxing District. Peripheral venous blood of the proband and his relatives were collected. Gene sequencing was performed by DNA exon sequencing, and head MRI+MRA was performed.

Results

Gene sequencing showed that the patient and his mother, brother, cousin, grandmother, aunt, cousin, uncle, and nephew carried c.14399A＞G (p.N4800S) heterozygous variants of RNF213 gene. The patient's father, daughter, and nephew did not have this RNF213 variant. Imaging examination found that the proband, his brother, and cousin had moyamoya disease.

Conclusion

RNF213 may be a rare pathogenic gene of moyamoya disease in Han population.

Key words: Moyamoya disease, RNF 213, Genetics, Stroke, Genetic variation

图2 烟雾病先证者哥哥和表哥磁共振血管造影（MRA）和数字减影血管造影（DSA）图像。先证者哥哥头MRA示双侧颈动脉末端闭塞（图a），DSA检查提示右侧颈动脉末端（图b）及左侧颈动脉末端闭塞（图c），可见烟雾状血管影；先证者表哥DSA检查提示右侧大脑中动脉重度狭窄（图d）及左侧大脑中动脉未见异常（图e），5年后头MRA检查示右侧颈动脉末端闭塞，左侧大脑中动脉重度狭窄（图f）

图3 烟雾病一家系系谱图注：圆圈和正方形分别代表女性和男性。黑色圆圈及黑色正方形表示确诊的烟雾病患者，箭头表示烟雾病先证者，斜线表示该患者已经去世。+/-，表示RNF213基因中c.14399A＞G的杂合变体；-/-为正常的RNF213基因

图4 烟雾病一家系RNF213基因的测序结果。图a：家系中RNF213基因发生c.14399A＞G错义变异，基因型为A/G型。图b：家系中RNF213基因未发生错义变异，基因型为A/A型

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A novel missense variant of RNF213 in a family with moyamoya disease: A case report and literature review

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A novel missense variant of RNF213 in a family with moyamoya disease: A case report and literature review