Genetics and Biomarkers of Moyamoya Disease: Significance of<i>RNF213</i>as a Susceptibility Gene

Fujimura, Miki; Sonobe, Shinya; Nishijima, Yasuo; Niizuma, Kuniyasu; Sakata, Hiroyuki; Kure, Shigeo; Tominaga, Teiji

doi:10.5853/jos.2014.16.2.65

Cited by 141 publications

(118 citation statements)

References 43 publications

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“…With difficulty in obtaining pathological findings, identification of susceptibility gene, such as RNF213, may further consolidate the diagnosis of MMD. 34 The gene tests were available only recently in our center, and we were able to identify only 3 patients who showed positivity. Further studies on MMD patients are required that used both HR-MRI and gene tests.…”

Section: Discussionmentioning

confidence: 90%

Isolated MCA Disease in Patients Without Significant Atherosclerotic Risk Factors

Ahn

Lee

Kim

et al. 2015

Stroke

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Background and Purpose-Diagnosis of intracranial artery atherosclerosis remains often uncertain. The high-resolution magnetic resonance imaging (HR-MRI) enables vessel wall assessment for more precise diagnoses. The aim of the present study was to investigate the etiologies of middle cerebral artery steno-occlusive disease in young adult patients with few atherosclerotic risk factors using HR-MRI. Methods-We prospectively studied patients who visited a tertiary hospital in Seoul, Korea, and had (1) unilateral middle cerebral artery disease (≥50% stenosis or occlusion), (2) were ≤55 years old and had no or minimal (≤1) atherosclerotic risk factors. We excluded patients with a confirmed diagnosis of Moyamoya disease, vasculitis, or dissection and those having emboligenic sources. A presumptive diagnosis was made based on HR-MRI findings, and patients were categorized as HR-athero (atherosclerotic disease), HR-MMD (Moyamoya disease), HR-dissection, or HR-vasculitis. Results-Among 95 patients analyzed, 26 (27.4%) had HR-athero who were more often male (P=0.004), smokers (P=0.018), and had focal stenosis (P=0.003) than others. As compared with the HR-athero patients, 29 HR-MMD patients were more often female (P<0.001) and more often had occlusive lesions (P=0.001) and nonfocal stenosis (P<0.001). The 22 HRdissection patients tended to have hypertension less often, and the 13 HR-vasculitis patients were younger (P=0.004) and tended to have nonfocal stenosis. Conclusions-In our cohort of young patients with minimal risk factors, atherosclerosis seems to be an uncommon pathology of middle cerebral artery stenosis. HR-MRI aids us to make a more reliable diagnosis.

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Section: Discussionmentioning

confidence: 90%

Isolated MCA Disease in Patients Without Significant Atherosclerotic Risk Factors

Ahn

Lee

Kim

et al. 2015

Stroke

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“…However, after carotid artery ligation, knockout mice did not present the transitory intimal and medial hyperplasia found in their wild-type littermates and had significantly thinner intimal and medial layers than wild type mice, suggesting a possible role of RNF213 in arterial wall remodeling [91] . Finally, recent experimental studies performed on p.R4810K-mutated cells showed a reduced angiogenic activity, and in another study, cycle cell perturbation with increased genomic stability [92,93] .…”

Section: Genome-wide Linkage Studiesmentioning

confidence: 86%

Research Progresses in Understanding the Pathophysiology of Moyamoya Disease

et al. 2016

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Background: The pathogenesis of moyamoya disease (MMD) is still unknown. The detection of inflammatory molecules such as cytokines, chemokines and growth factors in MMD patients' biological fluids supports the hypothesis that an abnormal angiogenesis is implicated in MMD pathogenesis. However, it is unclear whether these anomalies are the consequences of the disease or rather causal factors as well as these mechanisms remain insufficient to explain the pathophysiology of MMD. The presence of a family history in about 9-15% of Asian patients, the highly variable incidence rate between different ethnic and sex groups and the age of onset support the role of genetic factors in MMD pathogenesis. However, although some genetic loci have been associated with MMD, few of them have been replicated in independent series. Recently, RNF213 gene was shown to be strongly associated with MMD occurrence with a founder effect in East Asian patients. However, the mechanisms leading from RNF213 mutations to MMD clinical features are still unknown. Summary: The research on pathogenic mechanism of MMD is in its infancy. MMD is probably a complex and heterogeneous disorder, including different phenotypes and genotypes, in which more than a single factor is implicated. Key Message: Since the diagnosis of MMD is rapidly increasing worldwide, the development of more efficient stratifying risk systems, including both clinical but also biological drivers became imperative to improve our ability of predict prognosis and to develop mechanism-tailored interventions.

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“…Several genetic factors, especially the role of RNF123 mutation, have increasingly been analyzed in MMD with emphasis on ethnic differences [28][29][30][31] . Genetic factors in Moyamoya syndrome are more heterogenic [29] and the role of RNF123 mutation seems to be dependent on possible underlying pathology [32,33] .…”

Section: Discussionmentioning

confidence: 99%

Characterization of Clinical and Radiological Features of Quasi-Moyamoya Disease among European Caucasians Including Surgical Treatment and Outcome

Acker

Goerdes²,

Schmiedek³

et al. 2016

Cerebrovasc Dis

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Background: Moyamoya disease (MMD) associated with a potentially underlying disease, such as genetic disorders or other coexisting hematological pathologies, is called quasi-MMD. This very rare disease has been characterized mainly in Asian countries, so far. As MMD reveals several significant ethnic differences, the question is raised whether characteristics of quasi-MMD would also vary among different ethnic backgrounds. Here, we report a series of 61 patients with quasi-MMD and highlight the specific clinical features of this rare disease among European Caucasians. Methods: We retrospectively identified 61 European Caucasians with quasi-MMD who were treated in our institution between 1997 and 2014. We analyzed demographic data, clinical symptoms, associated diseases, angiographic characteristics and functional hemodynamic studies. Results: Thirty-three percent of our patients were juvenile. We observed an overall female predominance of 2.8:1. Seventy-nine percent presented with a typical quasi-MMD with more pronounced unilateral and atypical quasi-MMD in pediatric population (unilateral/atypical: pediatric patients 20/15%, adults 7/7%). We identified a wide range of associated diseases. Overall, 84 and 8% of our cohort presented initially with ischemic and hemorrhagic manifestation, respectively. The hemorrhagic manifestation of quasi-MMD occurred however only in adults. Angiographic analysis revealed steno-occlusive involvement of the posterior circulation (in addition to the anterior circulation) in 31% with a higher involvement in pediatric patients (40%) compared to adults (27%). Conclusions: The characterization of our European Caucasian cohort reveals several differences when compared to reported Asian quasi-MMD cohorts and also compared to European Caucasian MMD cohort. We conclude that quasi-MMD represents a distinct disease with different ethnic clinical features.

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Genetics and Biomarkers of Moyamoya Disease: Significance ofRNF213as a Susceptibility Gene

Cited by 141 publications

References 43 publications

Isolated MCA Disease in Patients Without Significant Atherosclerotic Risk Factors

Isolated MCA Disease in Patients Without Significant Atherosclerotic Risk Factors

Research Progresses in Understanding the Pathophysiology of Moyamoya Disease

Characterization of Clinical and Radiological Features of Quasi-Moyamoya Disease among European Caucasians Including Surgical Treatment and Outcome

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