Autosomal dominant moyamoya disease maps to chromosome 17q25.3

Mineharu, Yohei; Liu, W.; Inoue, Kazuhiro; Matsuura, Nobuki; Inoue, Sumiko; Takenaka, Katsunobu; Ikeda, Hidetoshi; Houkin, Kiyohiro; Takagi, Yasushi; Kikuta, Ken-ichiro; Nozaki, Kazuhiko; Hashimoto, Nobuo; Koizumi, Akio

doi:10.1212/01.wnl.0000291012.49986.f9

Cited by 149 publications

(101 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…These tests identified a single locus with a strong association with MMD (Po10 À8 ) on chromosome 17q25-ter (Figure 1b), which is in line with the latest mapping data of a MMD locus. 16 The SNP markers with Po10 À6 are listed in Table 1.…”

Section: Resultsmentioning

confidence: 99%

A genome-wide association study identifies RNF213 as the first Moyamoya disease gene

et al. 2010

View full text Add to dashboard Cite

Moyamoya disease (MMD) shows progressive cerebral angiopathy characterized by bilateral internal carotid artery stenosis and abnormal collateral vessels. Although B15% of MMD cases are familial, the MMD gene(s) remain unknown. A genome-wide association study of 785 720 single-nucleotide polymorphisms (SNPs) was performed, comparing 72 Japanese MMD patients with 45 Japanese controls and resulting in a strong association of chromosome 17q25-ter with MMD risk. This result was further confirmed by a locus-specific association study using 335 SNPs in the 17q25-ter region. A single haplotype consisting of seven SNPs at the RNF213 locus was tightly associated with MMD (P¼5.3Â10 À10 ). RNF213 encodes a really interesting new gene finger protein with an AAA ATPase domain and is abundantly expressed in spleen and leukocytes. An RNA in situ hybridization analysis of mouse tissues indicated that mature lymphocytes express higher levels of Rnf213 mRNA than their immature counterparts. Mutational analysis of RNF213 revealed a founder mutation, p.R4859K, in 95% of MMD families, 73% of non-familial MMD cases and 1.4% of controls; this mutation greatly increases the risk of MMD (P¼1.2Â10 À43 , odds ratio¼190.8, 95% confidence interval¼71.7-507.9). Three additional missense mutations were identified in the p.R4859K-negative patients. These results indicate that RNF213 is the first identified susceptibility gene for MMD.

show abstract

Section: Resultsmentioning

confidence: 99%

A genome-wide association study identifies RNF213 as the first Moyamoya disease gene

et al. 2010

View full text Add to dashboard Cite

show abstract

“…From these view points, several studies have been conducted by using a combination of several methods to specify the susceptibility gene for moyamoya disease (Table 6). 29,38,39,43,47) Of these, two independent groups from Japan have identified, very recently, the susceptibility gene for moyamoya disease by employing a combination of several methods, including linkage analysis, case-control association studies, and gene annotation studies. Thus, Kamada and colleagues from Tohoku University employed a genome-wide association study and identified ring finger protein (RNF) 213 ( * 613768; http://omim.org/entry/613768) as the first moyamoya disease gene.…”

Section: Geneticsmentioning

confidence: 99%

Review of Past Research and Current Concepts on the Etiology of Moyamoya Disease

Houkin

Ito

Sugiyama

et al. 2012

Neurol. Med. Chir.(Tokyo)

View full text Add to dashboard Cite

Research on moyamoya disease has progressed remarkably in the past several decades. Indeed, many new facts concerning the epidemiology of the disease have been revealed and surgical treatments have been drastically improved. However, despite extensive research, the mechanism of moyamoya disease is still unknown. Consequently, the cardinal treatment of this disease has not yet been developed. For further clarification of its etiology, innovative studies are therefore indispensable. The aim of this paper is to review research on the pathogenesis of moyamoya disease to identify milestones in the direction of its true solution. Many hypotheses of the pathogenesis of moyamoya disease have been proposed in the past half century, including infection (viral and bacterial), autoimmune disorders, proteins abnormality, and gene abnormality. Some of these are now considered to be historical achievements. Others, however, can be still subjected to contemporary research. Currently, several genetic abnormalities are considered to offer the most probable hypothesis. In addition, interesting papers have been presented on the role of the endothelial progenitor cell on the pathogenesis of moyamoya disease. Intuitively, however, it appears that a single theory cannot always explain the pathogenesis of this disease adequately. In other words, the complex mechanism of several factors may comprehensively explain the formation of moyamoya disease. The``double hit hypothesis'' is probably the best explanation for the complicated pathology and epidemiology of this disease.

show abstract

“…A number of genome-wide linkage studies have been performed in Japanese families with familial moyamoya that suggest linkage to 5 different chromosomal regions : 3p24.2-p26 7) , 6q25 8) , 8q23 16) , 12p12 16) , and 17q25 11,20) . Penetrance is in part age dependent and influenced by genomic imprinting 11) .…”

Section: Resultsmentioning

confidence: 99%

A Genome-Wide Study of Moyamoya-Type Cerebrovascular Disease in the Korean Population

Joo

Kim

Lee

et al. 2011

J Korean Neurosurg Soc

View full text Add to dashboard Cite

Objective : Structural genetic variation, including copy-number variation (CNV), constitutes a substantial fraction of total genetic variability, and the importance of structural variants in modulating susceptibility is increasingly being recognized. CNV can change biological function and contribute to pathophysiological conditions of human disease. Its relationship with common, complex human disease in particular is not fully understood. Here, we searched the human genome to identify copy number variants that predispose to moya-moya type cerebrovascular disease. Methods : We retrospectively analyzed patients who had unilateral or bilateral steno-occlusive lesions at the cerebral artery from March, 2007, to September, 2009. For the 20 subjects, including patients with moyamoya type pathologies and three normal healthy controls, we divided the subjects into 4 groups : typical moyamoya (n=6), unilateral moyamoya (n=9), progression unilateral to typical moyamoya (n=2) and non-moyamoya (n=3). Fragmented DNA was hybridized on Human610Quad v1.0 DNA analysis BeadChips (Illumina). Data analysis was performed with GenomeStudio v2009.1, Genotyping 1.1.9, cnvPartition_v2.3.4 software. Overall call rates were more than 99.8%. Results : In total, 1258 CNVs were identified across the whole genome. The average number of CNV was 45.55 per subject (CNV region was 45.4). The gain/loss of CNV was 52/249, having 4.7 fold higher frequencies in loss calls. The total CNV size was 904,657,868, and average size was 993,038. The largest portion of CNVs (613 calls) were 1M-10M in length. Interestingly, significant association between unilateral moyamoya disease (MMD) and progression of unilateral to typical moyamoya was observed. Conclusion : Significant association between unilateral MMD and progression of unilateral to typical moyamoya was observed. The finding was confirmed again with clustering analysis. These data demonstrate that certain CNV associate with moyamoya-type cerebrovascular disease.

show abstract

Autosomal dominant moyamoya disease maps to chromosome 17q25.3

Abstract: Our data suggest that there is a major gene locus for autosomal dominant moyamoya disease on chromosome 17q25.3.

Cited by 149 publications

References 18 publications

A genome-wide association study identifies RNF213 as the first Moyamoya disease gene

A genome-wide association study identifies RNF213 as the first Moyamoya disease gene

Review of Past Research and Current Concepts on the Etiology of Moyamoya Disease

A Genome-Wide Study of Moyamoya-Type Cerebrovascular Disease in the Korean Population

Contact Info

Product

Resources

About