{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T20:24:12Z","timestamp":1790627052656,"version":"4.1.0"},"reference-count":25,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2019,3,6]],"date-time":"2019-03-06T00:00:00Z","timestamp":1551830400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003500","name":"Universit\u00e0 degli Studi di Padova","doi-asserted-by":"publisher","award":["CPDA140508\/14"],"award-info":[{"award-number":["CPDA140508\/14"]}],"id":[{"id":"10.13039\/501100003500","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2019,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Neurofibromatosis type 1 (NF1) is an autosomal dominant condition caused by inactivating mutations of the <jats:italic>NF1<\/jats:italic> gene. The wide allelic heterogeneity of this condition, with more than 3,000 pathogenic variants reported so far, is paralleled by its high clinical variability, which is observed even within the same family. The definition of genotype\u2013phenotype correlations has been hampered by the complexity of the <jats:italic>NF1<\/jats:italic> gene and, although a few exceptions have been recognized, the clinical course remains unpredictable in most patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Sequencing of NF1 in patients with caf\u00e8\u2010au\u2010lait spots identified the c.3112A&gt;G variant. RNA analysis and a minigene assay were employed to investigate splicing.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Here we report a novel genotype\u2013phenotype correlation in NF1: the identification of the missense variant NM_000267.3:c.3112A&gt;G p.(Arg1038Gly) in seven individuals from two unrelated families with a mild phenotype. All the patients manifest caf\u00e8\u2010au\u2010lait spots without neurofibromas or other NF1\u2013associated complications, and Noonan syndrome features in most cases. The missense variant was not previously reported in available databases, segregates with the phenotype and involves a highly conserved residue. Both a minigene assay and patient's RNA analysis excluded an effect on splicing.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our data support the correlation of the p.Arg1038Gly missense substitution with the cutaneous phenotype without neurofibromas or other complications. This finding may have relevant implications for patients and genetic counseling, but also to get insights into the function of neurofibromin.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.616","type":"journal-article","created":{"date-parts":[[2019,3,7]],"date-time":"2019-03-07T05:10:40Z","timestamp":1551935440000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["The Arg1038Gly missense variant in the <i>NF1<\/i> gene causes a mild phenotype without neurofibromas"],"prefix":"10.1002","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5380-6265","authenticated-orcid":false,"given":"Eva","family":"Trevisson","sequence":"first","affiliation":[{"name":"Department of Women\u2019s and Children\u2019s Health, Clinical Genetics Unit University of Padova Padova Italy"},{"name":"Laboratorio di Genetica Clinica ed Epidemiologica Istituto di Ricerca Pediatrica, IRP Padova 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