{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T16:46:31Z","timestamp":1791305191206,"version":"4.3.1"},"reference-count":70,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2019,7,31]],"date-time":"2019-07-31T00:00:00Z","timestamp":1564531200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Pigmentary manifestations can represent an early clinical sign in children affected by Neurofibromatosis type 1 (NF1), Legius syndrome, and other neurocutaneous disorders. The differential molecular diagnosis of these pathologies is a challenge that can now be met by combining next generation sequencing of target genes with concurrent second-level tests, such as multiplex ligation-dependent probe amplification and RNA analysis. We clinically and genetically investigated 281 patients, almost all pediatric cases, presenting with either NF1 (n = 150), only pigmentary features (caf\u00e9 au lait macules with or without freckling; (n = 95), or clinical suspicion of other RASopathies or neurocutaneous disorders (n = 36). The causative variant was identified in 239 out of the 281 patients analyzed (85.1%), while 42 patients remained undiagnosed (14.9%). The NF1 and SPRED1 genes were mutated in 73.3% and 2.8% of cases, respectively. The remaining 8.9% carried mutations in different genes associated with other disorders. We achieved a molecular diagnosis in 69.5% of cases with only pigmentary manifestations, allowing a more appropriate clinical management of these patients. Our findings, together with the increasing availability and sharing of clinical and genetic data, will help to identify further novel genotype\u2013phenotype associations that may have a positive impact on patient follow-up.<\/jats:p>","DOI":"10.3390\/genes10080580","type":"journal-article","created":{"date-parts":[[2019,7,31]],"date-time":"2019-07-31T11:37:07Z","timestamp":1564573027000},"page":"580","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Clinical and Genetic Findings in Children with Neurofibromatosis Type 1, Legius Syndrome, and Other Related Neurocutaneous Disorders"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7806-263X","authenticated-orcid":false,"given":"Teresa","family":"Giugliano","sequence":"first","affiliation":[{"name":"Department of Precision Medicine, University of Campania \u201cLuigi Vanvitelli\u201d, Via L. De Crecchio 7, 80138 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4547-0500","authenticated-orcid":false,"given":"Claudia","family":"Santoro","sequence":"additional","affiliation":[{"name":"Departement of Women\u2019s and Children\u2019s Health and General and Specialized Surgery, University of Campania \u201cLuigi Vanvitelli\u201d, Via Luigi De Crecchio 2, 80138 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annalaura","family":"Torella","sequence":"additional","affiliation":[{"name":"Department of Precision Medicine, University of Campania \u201cLuigi Vanvitelli\u201d, Via L. De Crecchio 7, 80138 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9454-2964","authenticated-orcid":false,"given":"Francesca","family":"Del Vecchio Blanco","sequence":"additional","affiliation":[{"name":"Department of Precision Medicine, University of Campania \u201cLuigi Vanvitelli\u201d, Via L. De Crecchio 7, 80138 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Grandone","sequence":"additional","affiliation":[{"name":"Departement of Women\u2019s and Children\u2019s Health and General and Specialized Surgery, University of Campania \u201cLuigi Vanvitelli\u201d, Via Luigi De Crecchio 2, 80138 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Elena","family":"Onore","sequence":"additional","affiliation":[{"name":"Department of Precision Medicine, University of Campania \u201cLuigi Vanvitelli\u201d, Via L. De Crecchio 7, 80138 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7213-9277","authenticated-orcid":false,"given":"Mariarosa Anna Beatrice","family":"Melone","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences and Advanced Surgery, University of Campania \u201cLuigi Vanvitelli\u201d, Piazza L. Miraglia 2, 80138 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Straccia","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences and Advanced Surgery, University of Campania \u201cLuigi Vanvitelli\u201d, Piazza L. Miraglia 2, 80138 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Melis","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Naples \u201cFederico II\u201d, Via Pansini 5, 80131 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7798-4368","authenticated-orcid":false,"given":"Vincenzo","family":"Piccolo","sequence":"additional","affiliation":[{"name":"Dermatology Unit, University of Campania \u201cLuigi Vanvitelli\u201d, Via Pansini 5, 80131 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Limongelli","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, University of Campania \u201cLuigi Vanvitelli\u201d, Via L. Bianchi c\/o Ospedale Monaldi, 80131 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salvatore","family":"Buono","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, \"Santobono-Pausilipon\" Pediatric Hospital, Via Fiore 6, 80129 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silverio","family":"Perrotta","sequence":"additional","affiliation":[{"name":"Departement of Women\u2019s and Children\u2019s Health and General and Specialized Surgery, University of Campania \u201cLuigi Vanvitelli\u201d, Via Luigi De Crecchio 2, 80138 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3378-5006","authenticated-orcid":false,"given":"Vincenzo","family":"Nigro","sequence":"additional","affiliation":[{"name":"Department of Precision Medicine, University of Campania \u201cLuigi Vanvitelli\u201d, Via L. De Crecchio 7, 80138 Napoli, Italy"},{"name":"Telethon Institute of Genetics and Medicine (TIGEM), Via Campi Flegrei 34, 80078 Pozzuoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9418-125X","authenticated-orcid":false,"given":"Giulio","family":"Piluso","sequence":"additional","affiliation":[{"name":"Department of Precision Medicine, University of Campania \u201cLuigi Vanvitelli\u201d, Via L. De Crecchio 7, 80138 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,7,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1120","DOI":"10.1038\/ng2113","article-title":"Germline loss-of-function mutations in SPRED1 cause a neurofibromatosis 1-like phenotype","volume":"39","author":"Brems","year":"2007","journal-title":"Nat. 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