{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T11:02:36Z","timestamp":1789642956799,"version":"4.0.0"},"reference-count":22,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2017,9,15]],"date-time":"2017-09-15T00:00:00Z","timestamp":1505433600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2018,1]]},"abstract":"<jats:p>Neurofibromatosis type 1 (<jats:styled-content style=\"fixed-case\">NF1<\/jats:styled-content>) has long been considered a well\u2010defined, recognizable monogenic disorder, with neurofibromas constituting a pathognomonic sign. This dogma has been challenged by recent descriptions of patients with enlarged nerves or paraspinal tumors, suggesting that neurogenic tumors and hypertrophic neuropathy may be a complication of Noonan syndrome with multiple lentigines (NSML) or <jats:styled-content style=\"fixed-case\">RASopathy<\/jats:styled-content> phenotype. We describe a 15\u2010year\u2010old boy, whose mother previously received clinical diagnosis of <jats:styled-content style=\"fixed-case\">NF1<\/jats:styled-content> due to presence of bilateral cervical and lumbar spinal lesions resembling plexiform neurofibromas and features suggestive of NS. <jats:styled-content style=\"fixed-case\">NF1<\/jats:styled-content> molecular analysis was negative in the mother. The boy presented with Noonan features, multiple lentigines and pectus excavatum. Next\u2010generation sequencing analysis of all <jats:styled-content style=\"fixed-case\">RASopathy<\/jats:styled-content> genes identified p.<jats:styled-content style=\"fixed-case\">Ser548Arg<\/jats:styled-content> missense mutation in <jats:styled-content style=\"fixed-case\">SOS1<\/jats:styled-content> in the boy, confirmed in his mother. Brain and spinal magnetic resonance imaging scans were negative in the boy. No heart involvement or deafness was observed in proband or mother. This is the first report of a <jats:styled-content style=\"fixed-case\">SOS1<\/jats:styled-content> mutation associated with hypertrophic neuropathy resembling plexiform neurofibromas, a rare complication in Noonan phenotypes with mutations in <jats:styled-content style=\"fixed-case\">RASopathy<\/jats:styled-content> genes. Our results highlight the overlap between <jats:styled-content style=\"fixed-case\">RASopathies<\/jats:styled-content>, suggesting that <jats:styled-content style=\"fixed-case\">NF1<\/jats:styled-content> diagnostic criteria need rethinking. Genetic analysis of <jats:styled-content style=\"fixed-case\">RASopathy<\/jats:styled-content> genes should be considered when diagnosis is uncertain.<\/jats:p>","DOI":"10.1111\/cge.13047","type":"journal-article","created":{"date-parts":[[2017,4,29]],"date-time":"2017-04-29T18:38:26Z","timestamp":1493491106000},"page":"138-143","source":"Crossref","is-referenced-by-count":22,"title":["Multiple spinal nerve enlargement and <i><scp>SOS1<\/scp><\/i> mutation: Further evidence of overlap between neurofibromatosis type 1 and Noonan phenotype"],"prefix":"10.1111","volume":"93","author":[{"given":"C.","family":"Santoro","sequence":"first","affiliation":[{"name":"Dipartimento della Donna, del Bambino e della Chirurgia generale e specialistica Universit\u00e0 degli Studi della Campania \u201cLuigi Vanvitelli\u201d  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.","family":"Giugliano","sequence":"additional","affiliation":[{"name":"Dipartimento di Biochimica, Biofisica e Patologia Generale Universit\u00e0 degli Studi della Campania \u201cLuigi Vanvitelli\u201d  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.A.B.","family":"Melone","sequence":"additional","affiliation":[{"name":"Divisione di Neurologia, Dipartimento Medico\u2010Chirurgico di Internistica Clinica e Sperimentale \u201cF. Magrassi e A. Lanzara\u201d Universit\u00e0 degli Studi della Campania \u201cLuigi Vanvitelli\u201d  Naples Italy"},{"name":"Centro Interuniversitario di Ricerca in Neuroscienze (CIRN)  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Cirillo","sequence":"additional","affiliation":[{"name":"Prima Divisione di Neurologia, Dipartimento di Scienze Mediche, Chirurgiche, Neurologiche, Metaboliche e dell'Invecchiamento Universit\u00e0 degli Studi della Campania \u201cLuigi Vanvitelli\u201d  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Schettino","sequence":"additional","affiliation":[{"name":"Divisione di Neurologia, Dipartimento Medico\u2010Chirurgico di Internistica Clinica e Sperimentale \u201cF. Magrassi e A. Lanzara\u201d Universit\u00e0 degli Studi della Campania \u201cLuigi Vanvitelli\u201d  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Bernardo","sequence":"additional","affiliation":[{"name":"Dipartimento di Salute Mentale, Fisica e Medicina Preventiva, Clinica di Neuropsichiatria Infantile Universit\u00e0 degli Studi della Campania \u201cLuigi Vanvitelli\u201d  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Cirillo","sequence":"additional","affiliation":[{"name":"Prima Divisione di Neurologia, Dipartimento di Scienze Mediche, Chirurgiche, Neurologiche, Metaboliche e dell'Invecchiamento Universit\u00e0 degli Studi della Campania \u201cLuigi Vanvitelli\u201d  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Perrotta","sequence":"additional","affiliation":[{"name":"Dipartimento della Donna, del Bambino e della Chirurgia generale e specialistica Universit\u00e0 degli Studi della Campania \u201cLuigi Vanvitelli\u201d  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9418-125X","authenticated-orcid":false,"given":"G.","family":"Piluso","sequence":"additional","affiliation":[{"name":"Dipartimento di Biochimica, Biofisica e Patologia Generale Universit\u00e0 degli Studi della Campania \u201cLuigi Vanvitelli\u201d  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,9,15]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/jhg.2015.114"},{"key":"e_1_2_5_3_1","volume-title":"GeneReviews(R)","author":"Friedman JM","year":"1993"},{"key":"e_1_2_5_4_1","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1001\/archneur.1988.00520290115023","article-title":"Neurofibromatosis: conference statement","volume":"45","author":"National Institutes of Health Consensus Development C","year":"1988","journal-title":"Arch Neurol"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005537-200408000-00018"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22832"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1086\/510781"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2015.93"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2014.243"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng2113"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.37601"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2015-103177"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12883-015-0310-8"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.2011.01764.x"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1939"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.21492"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2350-15-14"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2350-15-44"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1218173110"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1926"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1601-183X.2008.00469.x"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0036-1579766"},{"key":"e_1_2_5_23_1","volume-title":"GeneReviews(R)","author":"Allanson JE","year":"1993"}],"container-title":["Clinical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fcge.13047","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cge.13047","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,30]],"date-time":"2023-09-30T01:59:56Z","timestamp":1696039196000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cge.13047"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,9,15]]},"references-count":22,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2018,1]]}},"alternative-id":["10.1111\/cge.13047"],"URL":"https:\/\/doi.org\/10.1111\/cge.13047","archive":["Portico"],"relation":{},"ISSN":["0009-9163","1399-0004"],"issn-type":[{"value":"0009-9163","type":"print"},{"value":"1399-0004","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,9,15]]}}}