J Stroke.  2014 May;16(2):65-72.

Genetics and Biomarkers of Moyamoya Disease: Significance of RNF213 as a Susceptibility Gene

• Fujimura M
• Sonobe S
• Nishijima
• Niizuma K
• Sakata H
• Kure S
• Tominaga T

Abstract

Moyamoya disease is characterized by a progressive stenosis at the terminal portion of the internal carotid artery and an abnormal vascular network at the base of the brain. Although its etiology is still unknown, recent genome-wide and locus-specific association studies identified RNF213 as an important susceptibility gene of moyamoya disease among East Asian population. A polymorphism in c.14576G>A in RNF213 was identified in 95% of familial patients with moyamoya disease and 79% of sporadic cases, and patients having this polymorphism were found to have significantly earlier disease onset and a more severe form of moyamoya disease, such as the presentation of cerebral infarction and posterior cerebral artery stenosis. The exact mechanism by which the RNF213 abnormality relates to moyamoya disease remains unknown, while recent reports using genetically engineered mice lacking RNF213 by homologous recombination provide new insight for the pathogenesis of this rare entity. Regarding biomarkers of moyamoya disease, moyamoya disease is characterized by an increased expression of angiogenic factors and pro-inflammatory molecules such as vascular endothelial growth factors and matrix metalloproteinase-9, which may partly explain its clinical manifestations of the pathologic angiogenesis, spontaneous hemorrhage, and higher incidence of cerebral hyperperfusion after revascularization surgery. More recently, blockade of these pro-inflammatory molecules during perioperative period is attempted to reduce the potential risk of surgical complication including cerebral hyperperfusion syndrome. In this review article, we focus on the genetics and biomarkers of moyamoya disease, and sought to discuss their clinical implication.

Keyword

Moyamoya disease; Genetics; Biomarkers; RNF213; Susceptibility gene

MeSH Terms

Angiogenesis Inducing Agents
Animals
Asian Continental Ancestry Group
Biomarkers*
Brain
Carotid Artery, Internal
Cerebral Infarction
Constriction, Pathologic
Genetics*
Hemorrhage
Homologous Recombination
Humans
Incidence
Matrix Metalloproteinase 9
Mice
Moyamoya Disease*
Neovascularization, Pathologic
Perioperative Period
Posterior Cerebral Artery
Vascular Endothelial Growth Factor A
Vascular Endothelial Growth Factors
Angiogenesis Inducing Agents
Matrix Metalloproteinase 9
Vascular Endothelial Growth Factor A
Vascular Endothelial Growth Factors