Abstract
RASopathies or RAS/mitogen-activated protein kinase (MAPK) syndromes are a group of phenotypically overlapping syndromes caused by germline mutations that encode components of the RAS/MAPK signaling pathway. These disorders include neurofibromatosis type I, Legius syndrome, Noonan syndrome, Noonan syndrome with multiple lentigines (formerly called LEOPARD syndrome), Costello syndrome, cardiofaciocutaneous (CFC) syndrome, Noonan-like syndrome, hereditary gingival fibromatosis and capillary malformation–arteriovenous malformation. Recently, novel gene variants, including RIT1, RRAS, RASA2, A2ML1, SOS2 and LZTR1, have been shown to be associated with RASopathies, further expanding the disease entity. Although further analysis will be needed, these findings will help to better elucidate an understanding of the pathogenesis of these disorders and will aid in the development of potential therapeutic approaches. In this review, we summarize the novel genes that have been reported to be associated with RASopathies and highlight the cardiovascular abnormalities that may arise in affected individuals.
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Acknowledgements
We thank members of the Department of Medical Genetics, Tohoku University School of Medicine, for contributing to RASopathy diagnostics and research. We are grateful to patients with RASopathies and their families and to the doctors who participated in our studies. This work was supported in part by grants from the Ministry of Health, Labour and Welfare of Japan, from the Practical Research Project for Rare/Intractable Diseases from Japan Agency for Medical Research and development, AMED, and from the Japan Society for the Promotion of Science (a Grant-in-Aid for Scientific Research (B)).
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Aoki, Y., Niihori, T., Inoue, Si. et al. Recent advances in RASopathies. J Hum Genet 61, 33–39 (2016). https://doi.org/10.1038/jhg.2015.114
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DOI: https://doi.org/10.1038/jhg.2015.114
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