Moyamoya Disease Explored Through RNF213 PDF – Genetics Molecular Pathology and Clinical Sciences
4.54 MB PDF
Preface
More than 60 years have passed since the first case of moyamoya disease was reported in 1955 by Japanese neurosurgeons. In the 1970s, this unique cerebrovascular occlusive disease was named moyamoya disease, and its distinctive-sounding name, together with the concomitant development of surgical treatments for moyamoya by Japanese surgeons, facilitated its international recognition. Further recognition for moyamoya was earned after the late 1980s by Japanese neurosurgeons through clinical epidemiological studies that suggested the involvement of genetic factors in the development of moyamoya and the demonstration that moyamoya was one of the major causes of stroke in the younger population. All these breakthroughs were made by pioneer neurosurgeon groups.
At the turn of the twenty-first century, I joined a research group on moyamoya disease as an expert of social medicine. The group was supported by the Ministry Health and Labor of Japan and organized by Dr. Nobuo Hashimoto, professor emeritus of Kyoto University and one of the most prominent neurosurgeons in Japan. He expected me as a social medicine researcher to expand the investigations on the genetic factor(s) involved with moyamoya in collaboration with neurosurgeons. Fortunately, in 2010 we were able to identify RNF213 R4810K (mysterin) as a genetic factor for moyamoya disease. (Please see Chapter 1 for the official report by this group.) However, elucidation of this genetic factor unveiled unexpected complexities: given that the carrier prevalence of RNF213 R4810K is 0.8–2.0% in the general population in East Asian countries, there is a large gap between the prevalence of moyamoya patients (roughly 1/10000 population) and carriers (1/50 in the general population). This discrepancy required a rational explanation and led us to postulate that there were additional factors, i.e., non-genetic factors, such as environmental factors or infection, for the development of moyamoya disease.
Such a gap also strongly implies that prevention of moyamoya disease can be best achieved by a high-risk strategy focusing on carriers. On the other hand, it raises additional unresolved questions: what is the health risk of R4810K for carriers, what is the function of RNF213, how does R4810K impair RNF213 functions, and how does it lead to moyamoya disease in concert with non-genetic factors?
Addressing such unresolved questions is not only interesting, but also critical for developing nonsurgical therapeutic approaches and disease-prevention strategies. Those unsolved mysteries for RNF213 need further expansion on the horizon of moyamoya disease with the combined efforts of molecular biologists and biochemists.
The aim of the present book is to provide the most up-to-date information on the role of RNF213 in moyamoya disease, not only for neurosurgeons, but also for public health researchers and basic biological scientists. Special emphasis, therefore, has been placed on a more comprehensive approach towards the clinical aspects, genetic epidemiology, and biochemical and physiological functions of RNF213. Contributors are well-known frontline clinical, social medicine, and molecular biology researchers of moyamoya disease and RNF213 in different disciplines beyond neurosurgery.
Current topics in our journal, i.e., Environmental Health and Preventive Medicine, published in partnership with the Japanese Society of Hygiene, aim to deliver cutting-edge information as explored by frontline experts from the around the globe in a diverse area of expertise, focusing on prevention of diseases and environmental health related to health risks. The book series is a valuable resource to researchers, clinicians, and administrators who are seeking comprehensive information on environmental health and health promotion. Therefore, I am very proud of this book, not only as a researcher in social medicine, but also as the president of the Japanese Society of Hygiene, because I am certain that our society can contribute to the prevention of moyamoya disease and clearly demonstrate a pivotal role of social medicine in modern health issues. Finally, all the contributors hope that this book stimulates research on vascular diseases through the study of RNF213 and paves the way to novel innovations for the prevention, treatment, and management of cerebrovascular diseases.
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