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Somatic\n                    <jats:italic>CBL<\/jats:italic>\n                    mutations play a driver role in a variety of cancers, particularly myeloid malignancies, whereas germline defects in the same gene underlie a RASopathy having clinical overlap with Noonan syndrome (NS) and predisposing to juvenile myelomonocytic leukemia and vasculitis. Other features of the disorder include cardiac defects, postnatal growth delay, cryptorchidism, facial dysmorphisms, and predisposition to develop autoimmune disorders. Here we report a novel\n                    <jats:italic>CBL<\/jats:italic>\n                    variant (c.1202G&gt;T; p.Cys401Phe) occurring\n                    <jats:italic>de novo<\/jats:italic>\n                    in a subject with caf\u00e9\u2010au\u2010lait macules, feeding difficulties, mild dysmorphic features, psychomotor delay, autism spectrum disorder, thrombocytopenia, hepatosplenomegaly, and recurrent hypertransaminasemia. The identified variant affects an evolutionarily conserved residue located in the RING finger domain, a known mutational hot spot of both germline and somatic mutations. Functional studies documented enhanced EGF\u2010induced ERK phosphorylation in transiently transfected COS1 cells. The present findings further support the association of pathogenic\n                    <jats:italic>CBL<\/jats:italic>\n                    variants with immunological and hematological manifestations in the context of a presentation with only minor findings reminiscent of NS or a clinically related RASopathy.\n                  <\/jats:p>","DOI":"10.1002\/ajmg.a.63627","type":"journal-article","created":{"date-parts":[[2024,4,13]],"date-time":"2024-04-13T01:55:06Z","timestamp":1712973306000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Immunological and hematological findings as major features in a patient with a new germline pathogenic\n                    <scp>\n                      <i>CBL<\/i>\n                    <\/scp>\n                    variant"],"prefix":"10.1002","volume":"194","author":[{"given":"Emilia","family":"Stellacci","sequence":"first","affiliation":[{"name":"Department of Oncology and Molecular Medicine Istituto Superiore di Sanit\u00e0  Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennefer N.","family":"Carter","sequence":"additional","affiliation":[{"name":"Stanford Center for Undiagnosed Diseases Stanford University  Stanford California USA"},{"name":"Department of Pediatrics \u2013 Medical Genetics Stanford University School of Medicine  Stanford California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luca","family":"Pannone","sequence":"additional","affiliation":[{"name":"Molecular Genetics and Functional Genomics Research Unit Ospedale Pediatrico Bambino Ges\u00f9, IRCCS  Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8601-0020","authenticated-orcid":false,"given":"David","family":"Stevenson","sequence":"additional","affiliation":[{"name":"Stanford Center for Undiagnosed Diseases Stanford University  Stanford California USA"},{"name":"Department of Pediatrics \u2013 Medical Genetics Stanford University School of Medicine  Stanford California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dorsa","family":"Moslehi","sequence":"additional","affiliation":[{"name":"Stanford Center for Undiagnosed Diseases Stanford University  Stanford California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Serenella","family":"Venanzi","sequence":"additional","affiliation":[{"name":"Department of Oncology and Molecular Medicine Istituto Superiore di Sanit\u00e0  Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"Undiagnosed Diseases Network","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5369-346X","authenticated-orcid":false,"given":"Jonathan A.","family":"Bernstein","sequence":"additional","affiliation":[{"name":"Stanford Center for Undiagnosed Diseases Stanford University  Stanford California USA"},{"name":"Department of Pediatrics \u2013 Medical Genetics Stanford University School of Medicine  Stanford California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7736-9672","authenticated-orcid":false,"given":"Marco","family":"Tartaglia","sequence":"additional","affiliation":[{"name":"Molecular Genetics and Functional Genomics Research Unit Ospedale Pediatrico Bambino Ges\u00f9, IRCCS  Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5843-419X","authenticated-orcid":false,"given":"Simone","family":"Martinelli","sequence":"additional","affiliation":[{"name":"Department of Oncology and Molecular Medicine Istituto Superiore di Sanit\u00e0  Rome 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