{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T11:29:43Z","timestamp":1791804583952,"version":"4.3.4"},"reference-count":44,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2021,6,29]],"date-time":"2021-06-29T00:00:00Z","timestamp":1624924800000},"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":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>RASopathies are a group of disorders caused by pathogenic variants in the genes encoding Ras\/mitogen\u2010activated protein kinase pathway and share overlapping clinical and molecular features. This study is aimed to describe the clinical and molecular features of 38 patients with RASopathies. Sanger or targeted next\u2010generation sequencing of related genes and multiplex ligation\u2010dependent\u2010probe amplification analysis for <jats:italic>NF1<\/jats:italic> were performed. The pathogenic variant detection rate was 94.4%. While <jats:italic>PTPN11<\/jats:italic> was responsible for 50% of 18 patients with Noonan syndrome (NS), <jats:italic>SOS1<\/jats:italic>, <jats:italic>LZTR1<\/jats:italic>, <jats:italic>RIT1<\/jats:italic>, and <jats:italic>RAF1<\/jats:italic> were responsible for the remaining 27.8%, 11.1%, 5.5%, and 5.5%, respectively. Three variants in <jats:italic>LZTR1<\/jats:italic> were novel, of which two were identified in the compound heterozygous state in a patient with intellectual disability and hypertrophic cardiomyopathy, whereas the third variant was found in the heterozygous state in a patient with pulmonary stenosis and normal intelligence. We described pyloric stenosis, knee dislocation, and cleft palate in patients with <jats:italic>SOS1<\/jats:italic>, <jats:italic>RIT1<\/jats:italic>, and <jats:italic>RAF1<\/jats:italic> variants, respectively, that was not previously reported. We detected a <jats:italic>PTPN11<\/jats:italic> variant in three patients from same family with NS with multiple lentigines. <jats:italic>BRAF<\/jats:italic> and <jats:italic>MAP2K2<\/jats:italic> variants were found in eight patients with Cardiofaciocutaneous syndrome. Two variants in <jats:italic>HRAS<\/jats:italic> were detected in two Costello syndrome patients, one with a mild and the other with a severe phenotype. While large <jats:italic>NF1<\/jats:italic> deletions were identified in four Neurofibromatosis\u2010NS patients with intellectual disability, intelligence was normal in one patient with missense variant. In conclusion, this study provided three novel variants in <jats:italic>LZTR1<\/jats:italic> and expanded the clinical phenotype of rare RASopathies.<\/jats:p>","DOI":"10.1002\/ajmg.a.62410","type":"journal-article","created":{"date-parts":[[2021,6,29]],"date-time":"2021-06-29T10:55:29Z","timestamp":1624964129000},"page":"3623-3633","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Expanding the clinical phenotype of <scp>RASopathies<\/scp> in 38 Turkish patients, including the rare <scp><i>LZTR1<\/i><\/scp>, <scp><i>RAF1<\/i><\/scp>, <scp><i>RIT1<\/i><\/scp> variants, and large deletion in <scp><i>NF1<\/i><\/scp>"],"prefix":"10.1002","volume":"185","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0495-6152","authenticated-orcid":false,"given":"Dilek","family":"Uluda\u011f Alkaya","sequence":"first","affiliation":[{"name":"Department of Pediatric Genetics Cerrahpasa Medical School, Istanbul University\u2010Cerrahpasa  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Lissewski","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, University Hospital Magdeburg  Magdeburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G\u00f6zde","family":"Ye\u015fil","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Medical School, Bezmialem University  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1618-9269","authenticated-orcid":false,"given":"Martin","family":"Zenker","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, University Hospital Magdeburg  Magdeburg 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