{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T20:24:09Z","timestamp":1790627049455,"version":"4.1.0"},"reference-count":45,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2020,6,19]],"date-time":"2020-06-19T00:00:00Z","timestamp":1592524800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of Health","award":["RF-2016-02361293 (to M.E. and F.N.)."],"award-info":[{"award-number":["RF-2016-02361293 (to M.E. and F.N.)."]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Neurofibromatosis type 1 (NF1) displays overlapping phenotypes with other neurocutaneous diseases such as Legius Syndrome. Here, we present results obtained using a next generation sequencing (NGS) panel including NF1, NF2, SPRED1, SMARCB1, and LZTR1 genes on Ion Torrent. Together with NGS, the Multiplex Ligation-Dependent Probe Amplification Analysis (MLPA) method was performed to rule out large deletions\/duplications in NF1 gene; we validated the MLPA\/NGS approach using Sanger sequencing on DNA or RNA of both positive and negative samples. In our cohort, a pathogenic variant was found in 175 patients; the pathogenic variant was observed in NF1 gene in 168 cases. A SPRED1 pathogenic variant was also found in one child and in a one year old boy, both NF2 and LZTR1 pathogenic variants were observed; in addition, we identified five LZTR1 pathogenic variants in three children and two adults. Six NF1 pathogenic variants, that the NGS analysis failed to identify, were detected on RNA by Sanger. NGS allows the identification of novel mutations in five genes in the same sequencing run, permitting unambiguous recognition of disorders with overlapping phenotypes with NF1 and facilitating genetic counseling and a personalized follow-up.<\/jats:p>","DOI":"10.3390\/genes11060671","type":"journal-article","created":{"date-parts":[[2020,6,19]],"date-time":"2020-06-19T10:43:58Z","timestamp":1592563438000},"page":"671","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Simultaneous Detection of NF1, SPRED1, LZTR1, and NF2 Gene Mutations by Targeted NGS in an Italian Cohort of Suspected NF1 Patients"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6313-0377","authenticated-orcid":false,"given":"Donatella","family":"Bianchessi","sequence":"first","affiliation":[{"name":"Molecular Neuro-Oncology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, via Celoria 11, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Cristina","family":"Ibba","sequence":"additional","affiliation":[{"name":"Molecular Neuro-Oncology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, via Celoria 11, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronica","family":"Saletti","sequence":"additional","affiliation":[{"name":"Developmental Neurology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, via Celoria 11, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0496-825X","authenticated-orcid":false,"given":"Stefania","family":"Blasa","sequence":"additional","affiliation":[{"name":"Molecular Neuro-Oncology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, via Celoria 11, 20133 Milan, Italy"},{"name":"Department of Biotechnology and Biosciences, University of Milano-Bicocca, Piazza dell\u2019Ateneo Nuovo, 1, 20126 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiziana","family":"Langella","sequence":"additional","affiliation":[{"name":"Molecular Neuro-Oncology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, via Celoria 11, 20133 Milan, Italy"},{"name":"Molecular Immunology Unit, Department of Research, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosina","family":"Paterra","sequence":"additional","affiliation":[{"name":"Molecular Neuro-Oncology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, via Celoria 11, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia Anna","family":"Cagnoli","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit, Woman-Child-Newborn Department, Fondazione IRCCS Ca\u2019 Granda-Ospedale Maggiore Policlinico, via Francesco Sforza 28, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Melloni","sequence":"additional","affiliation":[{"name":"Developmental Neurology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, via Celoria 11, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulietta","family":"Scuvera","sequence":"additional","affiliation":[{"name":"Pediatric Highly Intensive Care Unit, Universit\u00e0 degli Studi di Milano, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, via Francesco Sforza 28, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Natacci","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit, Woman-Child-Newborn Department, Fondazione IRCCS Ca\u2019 Granda-Ospedale Maggiore Policlinico, via Francesco Sforza 28, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Cesaretti","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit, Woman-Child-Newborn Department, Fondazione IRCCS Ca\u2019 Granda-Ospedale Maggiore Policlinico, via Francesco Sforza 28, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaetano","family":"Finocchiaro","sequence":"additional","affiliation":[{"name":"Molecular Neuro-Oncology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, via Celoria 11, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4744-9377","authenticated-orcid":false,"given":"Marica","family":"Eoli","sequence":"additional","affiliation":[{"name":"Molecular Neuro-Oncology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, via Celoria 11, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,6,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/0092-8674(90)90253-B","article-title":"A major segment of the neurofibromatosis type 1 gene: cDNA sequence, genomic structure, and point mutations","volume":"62","author":"Cawthon","year":"1990","journal-title":"Cell"},{"key":"ref_2","unstructured":"Kaufmann, D. 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