{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T12:19:04Z","timestamp":1787660344368,"version":"build-2736575974"},"reference-count":51,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2021,9,3]],"date-time":"2021-09-03T00:00:00Z","timestamp":1630627200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Genes Chromosomes &amp; Cancer"],"published-print":{"date-parts":[[2022,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Neurofibromatosis type I, a genetic condition due to pathogenic variants in the <jats:italic>NF1<\/jats:italic> gene, is burdened by a high rate of complications, including neoplasms, which increase morbidity and mortality for the disease. We retrospectively re\u2010evaluated the <jats:italic>NF1<\/jats:italic> gene variants found in the period 2000\u20132019 and we studied for genotype\/phenotype correlations of disease complications and neoplasms 34 variants, which were shared by at least two unrelated families (range 2\u201311) for a total 141 of probands and 21 relatives affected by Neurofibromatosis type I. Recurrent variants could be ascribed to the most common mutational mechanisms (C to T transition, microsatellite slippage, non\u2010homologous recombination). In genotype\/phenotype correlations, the variants p.Arg440*, p.Tyr489Cys, and p.Arg1947*, together with the gross gene deletions, displayed the highest rates of complications. When considering neoplasms, carriers of variants falling in the extradomain region at the 5\u2032 end of <jats:italic>NF1<\/jats:italic> had a lower age\u2010related cancer frequency than the rest of the gene sequence, showing a borderline significance (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.045), which was not conserved after correction with covariates. We conclude that (1) hotspots in <jats:italic>NF1<\/jats:italic> occur via different mutational mechanisms, (2) several variants are associated with high rates of complications and cancers, and (3) there is an initial evidence toward a lower cancer risk for carriers of variants in the 5\u2032 end of the <jats:italic>NF1<\/jats:italic> gene although not significant at the multivariate analysis.<\/jats:p>","DOI":"10.1002\/gcc.22997","type":"journal-article","created":{"date-parts":[[2021,8,24]],"date-time":"2021-08-24T15:10:12Z","timestamp":1629817812000},"page":"10-21","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Recurrent <i>NF1<\/i> gene variants and their genotype\/phenotype correlations in patients with Neurofibromatosis type I"],"prefix":"10.1002","volume":"61","author":[{"given":"Matteo","family":"Riva","sequence":"first","affiliation":[{"name":"Medical Genetics, Department of Medicine and Surgery University of Parma  Parma Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davide","family":"Martorana","sequence":"additional","affiliation":[{"name":"University Hospital of Parma  Parma Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vera","family":"Uliana","sequence":"additional","affiliation":[{"name":"University Hospital of Parma  Parma Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edoardo","family":"Caleffi","sequence":"additional","affiliation":[{"name":"Plastic Surgery, University Hospital of Parma  Parma Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Boschi","sequence":"additional","affiliation":[{"name":"Plastic Surgery, University Hospital of Parma  Parma Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Livia","family":"Garavelli","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit, Azienda USL\u2010IRCCS  Reggio Emilia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Ponti","sequence":"additional","affiliation":[{"name":"Division of Clinical Pathology University of Modena and Reggio Emilia  Modena Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Sangiorgi","sequence":"additional","affiliation":[{"name":"Medical Genetics and Skeletal Rare Diseases, Istituto Ortopedico Rizzoli  Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudio","family":"Graziano","sequence":"additional","affiliation":[{"name":"Medical Genetics, S. 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