{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T02:56:41Z","timestamp":1774061801006,"version":"3.50.1"},"reference-count":15,"publisher":"Wiley","license":[{"start":{"date-parts":[[2023,4,28]],"date-time":"2023-04-28T00:00:00Z","timestamp":1682640000000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Human Mutation"],"published-print":{"date-parts":[[2023,4,28]]},"abstract":"<jats:p>Neurofibromatosis type 1 (NF1) is a neurocutaneous genetic disorder with a broad spectrum of associated signs and symptoms, including skeletal anomalies. The association of NF1 with anterior chest wall deformities has been recently reported, especially the pectus excavatum (PE). Over the years, several authors have suggested loss of heterozygosity (LOH) as the possible pathogenic mechanism underlying the development of the typical NF1 skeletal features. Here, we report a NF1 patient with severe chest deformity and harboring the germline heterozygous pathogenic NF1 variant NM_001042492.3: c.4271delC p.(Ala1424Glufs<jats:inline-formula>\n                     <a:math xmlns:a=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M1\">\n                        <a:msup>\n                           <a:mrow\/>\n                           <a:mrow>\n                              <a:mo>\u2217<\/a:mo>\n                           <\/a:mrow>\n                        <\/a:msup>\n                     <\/a:math>\n                  <\/jats:inline-formula>4). Through next-generation sequencing (NGS), we investigated the affected cartilage from the PE deformity and identified the additional frameshift variant NM_001042492.3: c.2953delC p.(Gln985Lysfs<jats:inline-formula>\n                     <c:math xmlns:c=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M2\">\n                        <c:msup>\n                           <c:mrow\/>\n                           <c:mrow>\n                              <c:mo>\u2217<\/c:mo>\n                           <\/c:mrow>\n                        <\/c:msup>\n                     <\/c:math>\n                  <\/jats:inline-formula>7), occurring as a somatic NF1 second hit mutation. Exome sequencing confirmed the absence of additional variants of potential pathogenic relevance. Western blot analysis showed the absence of wild-type NF1 protein in the cartilage of the patient, consistent with a somatic double inactivation (SDI) of NF1. Taken together, our findings support the role of SDI in NF1-related PE, widening the spectrum of the pathophysiological mechanisms involved in NF1-related skeletal features.<\/jats:p>","DOI":"10.1155\/2023\/3160653","type":"journal-article","created":{"date-parts":[[2023,4,28]],"date-time":"2023-04-28T20:35:05Z","timestamp":1682714105000},"page":"1-7","source":"Crossref","is-referenced-by-count":6,"title":["Somatic Double Inactivation of NF1 Associated with NF1-Related Pectus Excavatum Deformity"],"prefix":"10.1155","volume":"2023","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2473-5282","authenticated-orcid":true,"given":"Cristina","family":"Chelleri","sequence":"first","affiliation":[{"name":"Pediatric Neurology and Neuromuscular Disorders Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy"},{"name":"Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genoa, Genoa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2194-7239","authenticated-orcid":true,"given":"Marcello","family":"Scala","sequence":"additional","affiliation":[{"name":"Pediatric Neurology and Neuromuscular Disorders Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy"},{"name":"Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genoa, Genoa, Italy"},{"name":"Medical Genetics Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8498-3750","authenticated-orcid":true,"given":"Patrizia","family":"De Marco","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6342-0705","authenticated-orcid":true,"given":"Vittorio","family":"Guerriero","sequence":"additional","affiliation":[{"name":"Pediatric Thoracic and Airway Surgery Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy"},{"name":"Pediatric Surgery Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3698-9319","authenticated-orcid":true,"given":"Marzia","family":"Ognibene","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7807-1322","authenticated-orcid":true,"given":"Francesca","family":"Madia","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7064-9628","authenticated-orcid":true,"given":"Sara","family":"Guerrisi","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8456-7706","authenticated-orcid":true,"given":"Marco","family":"Di Duca","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5197-4380","authenticated-orcid":true,"given":"Michele","family":"Torre","sequence":"additional","affiliation":[{"name":"Pediatric Thoracic and Airway Surgery Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy"},{"name":"Pediatric Surgery Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Serena","family":"Tamburro","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8112-4800","authenticated-orcid":true,"given":"Paolo","family":"Scudieri","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2815-6288","authenticated-orcid":true,"given":"Gianluca","family":"Piccolo","sequence":"additional","affiliation":[{"name":"Pediatric Neurology and Neuromuscular Disorders Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy"},{"name":"Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genoa, Genoa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4355-1446","authenticated-orcid":true,"given":"Girolamo","family":"Mattioli","sequence":"additional","affiliation":[{"name":"Pediatric Thoracic and Airway Surgery Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1086-2651","authenticated-orcid":true,"given":"Francesca","family":"Buffelli","sequence":"additional","affiliation":[{"name":"Clinical Pathology Unit, IRCCS Istituto Giannina Gaslini, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9524-8492","authenticated-orcid":true,"given":"Paolo","family":"Uva","sequence":"additional","affiliation":[{"name":"Genomic Facility, Istituto Italiano di Tecnologia, Genova, 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E. Kelly","year":"2012","edition":"7th"},{"key":"6","first-page":"S0392","article-title":"Pectus excavatum in neurofibromatosis type 1: single-center experience and review of the literature","volume":"10","author":"E. Miraglia","year":"2019","journal-title":"Giornale Italiano di Dermatologia e Venereologia"},{"key":"7","doi-asserted-by":"publisher","DOI":"10.1111\/apa.15529"},{"key":"8","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpedsurg.2021.04.016"},{"key":"9","doi-asserted-by":"publisher","DOI":"10.1086\/504441"},{"key":"10","doi-asserted-by":"publisher","DOI":"10.1007\/s12031-019-01277-0"},{"key":"11","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2008.274"},{"key":"12","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddr310"},{"key":"13","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-16399-y"},{"key":"14","volume-title":"Cellular pathology technique","author":"C. F. A. 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