{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T17:18:59Z","timestamp":1781198339079,"version":"3.54.1"},"reference-count":26,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2019,3,21]],"date-time":"2019-03-21T00:00:00Z","timestamp":1553126400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt C"],"published-print":{"date-parts":[[2019,6]]},"abstract":"<jats:p>RASopathies are a group of genetic disorders due to dysregulation of the RAS\u2010MAPK signaling pathway, which is important in regulating cell growth, proliferation, and differentiation. These include Noonan syndrome (NS), Noonan syndrome with multiple lentigines (NSML), cardiofaciocutaneous (CFC) syndrome, and Costello syndrome (CS), clinical manifestations include growth retardation, developmental delay, cardiac defects, and specific dysmorphic features. There were abundant publications describing the genotype and phenotype from the Western populations. However, detailed study of RASopathies in Chinese population is lacking. We present here the largest cohort of RASopathies ever reported in Chinese populations, detailing the mutation spectrum and clinical phenotypes of these patients. The Clinical Genetic Service, Department of Health, and Queen Mary Hospital are tertiary referral centers for genetic disorders in Hong Kong. We retrospectively reviewed all the genetically confirmed cases of RASopathies, including NS, NSML, CFC syndrome, and CS, over the past 29\u2009years (from 1989 to 2017). Analyses of the mutation spectrum and clinical phenotypes were performed. One hundred and ninety\u2010one ethnic Chinese patients with genetically confirmed RASopathies were identified, including 148 patients with NS, 23 NSML, 12 CFC syndrome, and eight CS. We found a lower incidence of hypertrophic cardiomyopathy in individuals with NSML (27.3%), and NS caused by <jats:italic>RAF1<\/jats:italic> mutations (62.5%). Another significant finding was for those NS patients with myeloproliferative disorder, the mutations fall within Exon 3 of <jats:italic>PTPN11<\/jats:italic> but not only restricted to the well\u2010known hotspots, that is, p.Asp61 and p.Thr731, which suggested that re\u2010evaluation of the current tumor surveillance recommendation maybe warranted.<\/jats:p>","DOI":"10.1002\/ajmg.c.31692","type":"journal-article","created":{"date-parts":[[2019,3,21]],"date-time":"2019-03-21T09:45:45Z","timestamp":1553161545000},"page":"208-217","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Genetic landscape of RASopathies in Chinese: Three decades' experience in Hong Kong"],"prefix":"10.1002","volume":"181","author":[{"given":"Kris P. 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Y.","family":"Mak","sequence":"additional","affiliation":[{"name":"Department of Paediatrics and Adolescent Medicine, LKS Faculty of Medicine The University of Hong Kong  HKSAR, Hong Kong"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9923-7424","authenticated-orcid":false,"given":"Shirley S. W.","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Health Clinical Genetic Service  HKSAR, Hong Kong"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edgar W. L.","family":"Hau","sequence":"additional","affiliation":[{"name":"Department of Health Clinical Genetic Service  HKSAR, Hong Kong"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David K. H.","family":"Chan","sequence":"additional","affiliation":[{"name":"Department of Health Clinical Genetic Service  HKSAR, Hong Kong"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen T. 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