Abstract
Almost 20 years after the first case reported in 1955, moyamoya disease (MMD) was still thought to be specific to Asian populations. During the past 60 years, however, MMD has become globally recognized and tremendous therapeutic advances have been made. In 2011, RNF213 (mysterin) was identified as the major susceptibility gene for MMD. RNF213 is a large protein (591 kDa) and contains both AAA+ ATPase and E3 ligase domains. The p.R4810K variant, a founder mutation common to East Asians, is found at a rate of 70–90% in Japanese and Korean MMD patients and even shows a 1–3% allelic frequency in the general Japanese and Korean populations. As only a minor proportion (approx. 1 out of 200) of carriers develop MMD, environmental factors are thought to be major contributors to the progress of MMD. Recent in vitro molecular studies have revealed that p.R4810K induces endothelial dysfunction, which may ultimately lead to arterial stenosis and development of moyamoya vessels. Furthermore, RNF213 is found to be involved in interferon (IFN), noncanonical wnt, and PTP1B/α-ketoglutarate-dependent dioxygenase signal cascades. Such pathways are known to be activated in response to environmental stress signals, such as infection, inflammation, or hypoxia, which may therefore be involved in promoting the development of MMD.
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Koizumi, A., Youssefian, S. (2017). A Prologue to Moyamoya Disease and RNF213 . In: Koizumi, A., et al. Moyamoya Disease Explored Through RNF213. Current Topics in Environmental Health and Preventive Medicine. Springer, Singapore. https://doi.org/10.1007/978-981-10-2711-6_1
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DOI: https://doi.org/10.1007/978-981-10-2711-6_1
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