RNF213 Rare Variants in Slovakian and Czech Moyamoya Disease Patients.
RNF213 Rare Variants in Slovakian and Czech Moyamoya Disease Patients.
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DOI：
10.1371/journal.pone.0164759
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Koizumi A
中科院分区：
文献类型：
--
作者：
Kobayashi H;Brozman M;Kyselová K;Viszlayová D;Morimoto T;Roubec M;Školoudík D;Petrovičová A;Juskanič D;Strauss J;Halaj M;Kurray P;Hranai M;Harada KH;Inoue S;Yoshida Y;Habu T;Herzig R;Youssefian S;Koizumi A
RNF213/Mysterin已被确定为烟雾病的易感基因，烟雾病是一种以威氏圈闭塞病变为特征的脑血管疾病。p.R4810K （rs112735431）变异是一种与东亚烟雾病密切相关的创始多态性。许多non-p。在白人烟雾病患者中发现了RNF213的R4810K罕见变异，尽管尚未在该人群中调查种族突变。在本研究中，我们筛选了19名斯洛伐克和捷克烟雾病患者的RNF213变异。在斯洛伐克和捷克共和国的18个先证和1个患有烟雾病的亲属中，共对69个RNF213编码外显子进行了直接测序。我们之前报道过一个先证者携带RNF213 p.D4013N。本研究的结果在4名患者中发现了除p.D4013N外的4种罕见变异（p.R4019C、p.E4042K、p.V4146A和p.W4677L）。P.V4146A为新突变，p.R4019C和p.E4042K为同一等位基因上的双突变。P.W4677L是一种罕见的单核苷酸多态性，在两名烟雾病患者和同一家系的一名未受影响的受试者中发现。功能分析显示，转染RNF213 p.D4013N、p.R4019C和p.V4146A的人脐静脉内皮细胞迁移明显降低，RNF213 p.V4146A显著减少管的形成，提示这些都是致病突变。本研究结果在22.2%的斯洛伐克和捷克烟雾病患者（4/18先证者）中发现RNF213罕见变异，证实RNF213也可能是相对较大的白人患者群体的主要致病基因。
RNF213/Mysterin has been identified as a susceptibility gene for moyamoya disease, a cerebrovascular disease characterized by occlusive lesions in the circle of Willis. The p.R4810K (rs112735431) variant is a founder polymorphism that is strongly associated with moyamoya disease in East Asia. Many non-p.R4810K rare variants of RNF213 have been identified in white moyamoya disease patients, although the ethnic mutations have not been investigated in this population. In the present study, we screened for RNF213 variants in 19 Slovakian and Czech moyamoya disease patients. A total of 69 RNF213 coding exons were directly sequenced in 18 probands and one relative who suffered from moyamoya disease in Slovakia and the Czech Republic. We previously reported one proband harboring RNF213 p.D4013N. Results from the present study identified four rare variants other than p.D4013N (p.R4019C, p.E4042K, p.V4146A, and p.W4677L) in four of the patients. P.V4146A was determined to be a novel de novo mutation, and p.R4019C and p.E4042K were identified as double mutations inherited on the same allele. P.W4677L, found in two moyamoya disease patients and an unaffected subject in the same pedigree, was a rare single nucleotide polymorphism. Functional analysis showed that RNF213 p.D4013N, p.R4019C and p.V4146A-transfected human umbilical vein endothelial cells displayed significant lowered migration, and RNF213 p.V4146A significantly reduced tube formation, indicating that these are disease-causing mutations. Results from the present study identified RNF213 rare variants in 22.2% (4/18 probands) of Slovakian and Czech moyamoya disease patients, confirming that RNF213 may also be a major causative gene in a relative large population of white patients.
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影响因子：
8.3
作者：
Cecchi AC;Guo D;Ren Z;Flynn K;Santos-Cortez RL;Leal SM;Wang GT;Regalado ES;Steinberg GK;Shendure J;Bamshad MJ;University of Washington Center for Mendelian Genomics;Grotta JC;Nickerson DA;Pannu H;Milewicz DM
通讯作者：
Milewicz DM
影响因子：
4.7
作者：
Koizumi A;Kobayashi H;Hitomi T;Harada KH;Habu T;Youssefian S
通讯作者：
Youssefian S
影响因子：
3.7
作者：
Liu W;Morito D;Takashima S;Mineharu Y;Kobayashi H;Hitomi T;Hashikata H;Matsuura N;Yamazaki S;Toyoda A;Kikuta K;Takagi Y;Harada KH;Fujiyama A;Herzig R;Krischek B;Zou L;Kim JE;Kitakaze M;Miyamoto S;Nagata K;Hashimoto N;Koizumi A
通讯作者：
Koizumi A
DOI：
10.1073/pnas.0730882100
发表时间：
2003-04-15
影响因子：
11.1
作者：
Sudhakar, A;Sugimoto, H;Kalluri, R
通讯作者：
Kalluri, R
影响因子：
--
作者：
SUZUKI, J;TAKAKU, A
通讯作者：
TAKAKU, A