{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T19:36:46Z","timestamp":1777923406541,"version":"3.51.4"},"reference-count":39,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2019,2,14]],"date-time":"2019-02-14T00:00:00Z","timestamp":1550102400000},"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 A"],"published-print":{"date-parts":[[2019,4]]},"abstract":"<jats:p>RASopathies are a group of developmental disorders caused by pathogenic variants in the RAS\u2010MAPK pathway. Cardiomyopathy is a major feature of this group of disorders, specifically hypertrophic cardiomyopathy (HCM). HCM can be the first presenting feature in individuals with RASopathies. We conducted a retrospective study of all individuals who have had a cardiomyopathy gene panel ordered through our institution to determine the prevalence of pathogenic or likely pathogenic variants in RAS pathway genes in individuals with cardiomyopathy. We evaluated variants in the following genes: <jats:italic>BRAF, CBL, HRAS, KRAS, MAP2K1, MAP2K2, NF1, NRAS, PTPN11, RAF1, SHOC2,<\/jats:italic> and <jats:italic>SOS1<\/jats:italic>. We reviewed 74 cases with cardiomyopathy, including 32 with HCM, 24 with dilated cardiomyopathy (DCM), nine with both left ventricular noncompaction (LVNC) and DCM, four with LVNC only, two with arrhythmogenic right ventricular cardiomyopathy (ARVC) and three with unspecified cardiomyopathy. We identified four patients (5.41%) with pathogenic or likely pathogenic variants in <jats:italic>HRAS, PTPN11<\/jats:italic> and <jats:italic>RAF1<\/jats:italic> (two individuals). Indication for testing for all four individuals was HCM. The prevalence of pathogenic or likely pathogenic variants in RASopathy genes in our HCM patient cohort is 12.5% (4\/32). We conclude that the RASopathy genes should be included on multi\u2010gene panels for cardiomyopathy to increase diagnostic yield for individuals with HCM.<\/jats:p>","DOI":"10.1002\/ajmg.a.61072","type":"journal-article","created":{"date-parts":[[2019,2,14]],"date-time":"2019-02-14T13:45:41Z","timestamp":1550151941000},"page":"608-614","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Prevalence of pathogenic and likely pathogenic variants in the RASopathy genes in patients who have had panel testing for cardiomyopathy"],"prefix":"10.1002","volume":"179","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0343-6083","authenticated-orcid":false,"given":"Deema","family":"Aljeaid","sequence":"first","affiliation":[{"name":"Division of Human Genetics Cincinnati Children's Hospital Medical Center  Cincinnati Ohio"},{"name":"Department of Genetics Medicine, Faculty of Medicine King Abdulaziz University  Jeddah Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5059-9264","authenticated-orcid":false,"given":"Ana Isabel","family":"Sanchez","sequence":"additional","affiliation":[{"name":"Division of Human Genetics Cincinnati Children's Hospital Medical Center  Cincinnati Ohio"},{"name":"Instituto de Gen\u00e9tica Humana Pontificia Universidad Javeriana  Bogot\u00e1 Colombia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emily","family":"Wakefield","sequence":"additional","affiliation":[{"name":"Division of Human Genetics Cincinnati Children's Hospital Medical Center  Cincinnati Ohio"},{"name":"RASopathies Program Cincinnati Children's Hospital Medical Center  Cincinnati Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah E.","family":"Chadwell","sequence":"additional","affiliation":[{"name":"Division of Human Genetics Cincinnati Children's Hospital Medical Center  Cincinnati Ohio"},{"name":"RASopathies Program Cincinnati Children's Hospital Medical Center  Cincinnati Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicole","family":"Moore","sequence":"additional","affiliation":[{"name":"Heart Institute Diagnostic Laboratory Cincinnati Children's Hospital Medical Center  Cincinnati Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlos E.","family":"Prada","sequence":"additional","affiliation":[{"name":"Division of Human Genetics Cincinnati Children's Hospital Medical Center  Cincinnati Ohio"},{"name":"RASopathies Program Cincinnati Children's Hospital Medical Center  Cincinnati Ohio"},{"name":"Department of Pediatrics University of Cincinnati College of Medicine  Cincinnati Ohio"},{"name":"Division de Genetica, Departamento de Pediatr\u00eda Hospital Internacional de Colombia  Bucaramanga Colombia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenying","family":"Zhang","sequence":"additional","affiliation":[{"name":"Division of Human Genetics Cincinnati Children's Hospital Medical Center  Cincinnati Ohio"},{"name":"Heart Institute Diagnostic Laboratory Cincinnati Children's Hospital Medical Center  Cincinnati Ohio"},{"name":"Department of Pediatrics University of Cincinnati College of Medicine  Cincinnati Ohio"},{"name":"Laboratory of Genetics and Genomics Cincinnati Children's Hospital Medical Center  Cincinnati Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,2,14]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/00006254-198601000-00014"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1641"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.38178"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.23535"},{"issue":"5","key":"e_1_2_7_6_1","first-page":"e001768","article-title":"A comparison of whole genome sequencing to multigene panel testing in hypertrophic cardiomyopathy PatientsCLINICAL PERSPECTIVE","volume":"10","author":"Cirino A. 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