{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T08:02:59Z","timestamp":1780473779978,"version":"3.54.1"},"reference-count":46,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T00:00:00Z","timestamp":1773878400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T00:00:00Z","timestamp":1773878400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    RASopathies are a group of genetically heterogeneous developmental disorders caused by germline variants affecting the RAS\/MAPK signaling pathway. These disorders display overlapping clinical features and diverse molecular mechanisms. This study aimed to evaluate the clinical and molecular spectrum of patients diagnosed with RASopathies, with a particular focus on novel and rare variants. A retrospective, multicenter study was conducted on patients with clinically suspected RASopathy and diagnosed by targeted Next Generation Sequencing analysis between 2021 and 2024. Variants were classified according to ACMG criteria, and clinical data were reviewed for genotype\u2013phenotype correlations. Among 23 patients (14 males, 9 females), 15 (65.2%) had Noonan syndrome, five (21.7%) Neurofibromatosis Type 1, two (8.7%) Cardio\u2010facio\u2010cutaneous syndrome, and one (4.3%) Neurofibromatosis\u2013Noonan syndrome. The most frequent clinical findings were craniofacial dysmorphism (91.3%), musculoskeletal anomalies (82.6%), and cutaneous features (78.3%). A total of 24 heterozygous variants were identified in seven genes:\n                    <jats:italic>PTPN11<\/jats:italic>\n                    (45.8%),\n                    <jats:italic>NF1<\/jats:italic>\n                    (25%),\n                    <jats:italic>LZTR1<\/jats:italic>\n                    (12.5%), and\n                    <jats:italic>RASA2, SOS1, MAP2K1<\/jats:italic>\n                    , and\n                    <jats:italic>BRAF<\/jats:italic>\n                    (each 4.2%). Four novel variants were detected (\n                    <jats:italic>PTPN11<\/jats:italic>\n                    c.853\u2009+\u20094A&gt;G,\n                    <jats:italic>RASA2<\/jats:italic>\n                    p.E71D,\n                    <jats:italic>NF1<\/jats:italic>\n                    p.W784Mfs*10,\n                    <jats:italic>MAP2K1<\/jats:italic>\n                    p.A106T). This study highlights the clinical and molecular heterogeneity of RASopathies and expands the variant spectrum with novel and rare pathogenic alterations. The identification of new variants, particularly in rarely implicated genes such as\n                    <jats:italic>RASA2<\/jats:italic>\n                    , underlines the diagnostic value of comprehensive NGS\u2010based testing and the need for individualized, multidisciplinary clinical management.\n                  <\/jats:p>","DOI":"10.1111\/cge.70162","type":"journal-article","created":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T11:47:32Z","timestamp":1773920852000},"page":"36-45","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Novel Variants in\n                    <scp>\n                      <i>PTPN11<\/i>\n                    <\/scp>\n                    ,\n                    <scp>\n                      <i>NF1<\/i>\n                    <\/scp>\n                    ,\n                    <scp>\n                      <i>RASA2<\/i>\n                    <\/scp>\n                    , and\n                    <scp>\n                      <i>MAP2K1<\/i>\n                    <\/scp>\n                    : Expanding the Molecular Spectrum of\n                    <scp>RASopathies<\/scp>\n                    in a Turkish Cohort"],"prefix":"10.1111","volume":"110","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2735-6739","authenticated-orcid":false,"given":"Hatice","family":"Kocak Eker","sequence":"first","affiliation":[{"name":"Department of Medical Genetics Konya City Hospital  Konya Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2345-4382","authenticated-orcid":false,"given":"Tugba","family":"Ak\u0131n Duman","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Konya City Hospital  Konya Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8130-9792","authenticated-orcid":false,"given":"Fahrettin","family":"Duymus","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Department of Medical Genetics U\u015fak University  U\u015fak Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9012-9307","authenticated-orcid":false,"given":"Muserref","family":"Basdemirci","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Konya City Hospital  Konya Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3023-302X","authenticated-orcid":false,"given":"Busra","family":"Eser Cavdartepe","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Konya City Hospital  Konya Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8203-3572","authenticated-orcid":false,"given":"Nurdan","family":"\u00c7iftci","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology Konya City Hospital  Konya Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7729-3970","authenticated-orcid":false,"given":"Levent","family":"Simsek","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Sancaktepe \u015eehit Prof. Dr. \u0130lhan Varank Training and Research Hospital  \u0130stanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,3,19]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1242\/dmm.049344"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev\u2010genom\u2010091212\u2010153523"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gde.2009.04.001"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/mgg3.1180"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.c.32015"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22832"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2014.243"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078\u20100432.CCR\u201024\u20101611"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26083515"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.c.32012"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(12)61023\u2010X"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.13588"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40142\u2010016\u20100100\u20107"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1242\/dmm.049107"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes15030345"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.23624"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010018\u201020894\u20100"},{"issue":"2","key":"e_1_2_12_19_1","first-page":"92","article-title":"RASopathies: Neuro\u2010Cardio\u2010Facio\u2010Cutaneous Syndromes","volume":"7","author":"Utine G. E.","year":"2011","journal-title":"T\u00fcrkiye Klinikleri Journal of Pediatrics Science"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2011.05.024"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2009\u20103207"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2015-103018"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.anpede.2020.04.009"},{"key":"e_1_2_12_24_1","unstructured":"ClinGen The Clinical Genome Resource (ClinGen)(2018) https:\/\/clinicalgenome.org."},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010025\u201090635\u20107"},{"key":"e_1_2_12_26_1","unstructured":"ClinVar NF1 (gene)\u2014ClinVar. National Center for Biotechnology Information. 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