{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T05:18:40Z","timestamp":1787894320481,"version":"build-2784847793"},"reference-count":43,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T00:00:00Z","timestamp":1767744000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T00:00:00Z","timestamp":1767744000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100014653","name":"Manchester Biomedical Research Centre","doi-asserted-by":"publisher","award":["NIHR203308"],"award-info":[{"award-number":["NIHR203308"]}],"id":[{"id":"10.13039\/100014653","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    RASopathies are clinically overlapping neurodevelopmental syndromes resulting from germline mutations in genes involved in the rat sarcoma\/mitogen\u2010activated protein kinases (RAS\/MAPK) pathway. Historically, RASopathies have been described by clinical phenotypes, such as Noonan syndrome and Neurofibromatosis type I. There is emerging evidence of the association between Noonan syndrome spectrum disorders (NSSD) and systemic lupus erythematosus (SLE). Here, we present an SLE patient diagnosed with\n                    <jats:italic>SOS1\u2010<\/jats:italic>\n                    associated Noonan Syndrome (c.806\u2009T&gt;C; p.Met269Thr) as part of a research study. Reviewing the literature, we identified further 16 cases of NSSD associated with SLE. Nine out of 16 cases (56%) had a confirmed molecular diagnosis, with pathogenic missense variants identified in\n                    <jats:italic>KRAS, PTPN11<\/jats:italic>\n                    , and\n                    <jats:italic>SHOC2<\/jats:italic>\n                    genes, the majority in the last. Variants in\n                    <jats:italic>SHOC2<\/jats:italic>\n                    are the cause of only a small proportion of all presentations of NSSD. Our case represents the first reported case of SLE in a patient with a\n                    <jats:italic>SOS1<\/jats:italic>\n                    pathogenic variant. Compared to the general SLE population, SLE in the presence of NSSD develops at a younger age, with a similar prevalence among females and males, suggesting a contribution of the RAS\/MAPK pathway in the development of SLE.\n                  <\/jats:p>","DOI":"10.1002\/ajmga.70035","type":"journal-article","created":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T09:29:15Z","timestamp":1767778155000},"page":"1091-1097","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Noonan Syndrome Spectrum Disorders Predispose to Systemic Lupus Erythematosus: Case Report and Critical Review of the Literature"],"prefix":"10.1002","volume":"200","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7382-9958","authenticated-orcid":false,"given":"Anastasia\u2010Vasiliki","family":"Madenidou","sequence":"first","affiliation":[{"name":"Centre for Musculoskeletal Research The University of Manchester  Manchester UK"},{"name":"The Kellgren Centre for Rheumatology, Manchester Royal Infirmary, Manchester University NHS Foundation Trust  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gillian I.","family":"Rice","sequence":"additional","affiliation":[{"name":"Division of Evolution, Infection and Genomic Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health University of Manchester  Manchester UK"},{"name":"Manchester Centre for Genomic Medicine, Saint Mary's Hospital, Manchester University Hospitals NHS Foundation Trust  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"O'Sullivan","sequence":"additional","affiliation":[{"name":"Division of Evolution, Infection and Genomic Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health University of Manchester  Manchester UK"},{"name":"Manchester Centre for Genomic Medicine, Saint Mary's Hospital, Manchester University Hospitals NHS Foundation Trust  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben","family":"Parker","sequence":"additional","affiliation":[{"name":"The Kellgren Centre for Rheumatology, Manchester Royal Infirmary, Manchester University NHS Foundation Trust  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian N.","family":"Bruce","sequence":"additional","affiliation":[{"name":"Centre for Musculoskeletal Research The University of Manchester  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Burkitt\u2010Wright","sequence":"additional","affiliation":[{"name":"Division of Evolution, Infection and Genomic Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health University of Manchester  Manchester UK"},{"name":"Manchester Centre for Genomic Medicine, Saint Mary's Hospital, Manchester University Hospitals NHS Foundation Trust  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tracy A.","family":"Briggs","sequence":"additional","affiliation":[{"name":"Division of Evolution, Infection and Genomic Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health University of Manchester  Manchester UK"},{"name":"Manchester Centre for Genomic Medicine, Saint Mary's Hospital, Manchester University Hospitals NHS Foundation Trust  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,1,7]]},"reference":[{"key":"e_1_2_11_2_1","unstructured":"Adam M. P. S.Bick G. M.Mirzaa et\u00a0al. eds. n.d.\u201cNoonan Syndrome.\u201dAccessed February 19 2025.https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK1124\/."},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00296-011-1966-z"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.mcd.0000127467.04018.6d"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1177\/0961203316644333"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1054-139X(02)00364-6"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semarthrit.2013.04.009"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2665-9913(19)30142-0"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM197502202920822"},{"key":"e_1_2_11_10_1","first-page":"1","article-title":"Noonan Syndrome and Systemic Lupus Erythematosus: Association or Risk Factor?","volume":"1","author":"Cerpa\u2010Cruz S.","year":"2013","journal-title":"Journal of Clinical & Medical Genomics"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.425"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10067-003-0764-8"},{"issue":"2","key":"e_1_2_11_13_1","first-page":"E9","article-title":"Neurofibromatosis Type 1 in the Setting of Systemic Lupus Erythematosus","volume":"103","author":"Dhandha M. 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A Clinical Guideline Noonan Syndrome Guideline Development Group.\u201dAccessed March 14 2025.https:\/\/rasopathiesnet.org\/wp\u2010content\/uploads\/2014\/01\/265_Noonan_Guidelines.pdf."},{"key":"e_1_2_11_31_1","unstructured":"OMIM. n.d.\u201cOnline Mendelian Inheritance in Man.\u201dAccessed January 17 2025.https:\/\/omim.org\/help\/about."},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2022.577917"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.2478\/rir-2023-0022"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.35290"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780260427"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1151246"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.2012.01875.x"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2019.108274"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-08-301515"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.c.32012"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.beem.2010.09.002"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1939"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.38834"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1136\/lupus-2024-001345"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmga.70035","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ajmga.70035","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmga.70035","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T04:44:13Z","timestamp":1787892253000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmga.70035"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,7]]},"references-count":43,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,5]]}},"alternative-id":["10.1002\/ajmga.70035"],"URL":"https:\/\/doi.org\/10.1002\/ajmga.70035","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,7]]},"assertion":[{"value":"2025-04-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-15","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-07","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}