{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,3]],"date-time":"2026-05-03T14:08:38Z","timestamp":1777817318351,"version":"3.51.4"},"reference-count":18,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2015,11,12]],"date-time":"2015-11-12T00:00:00Z","timestamp":1447286400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2015,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:label\/><jats:p>Neurofibromatosis type 1 (<jats:styled-content style=\"fixed-case\">NF<\/jats:styled-content>1) is an autosomal dominant genetic condition caused by dominant loss\u2010of\u2010function mutations of the tumor suppressor gene <jats:italic><jats:styled-content style=\"fixed-case\">NF<\/jats:styled-content>1<\/jats:italic> that encodes neurofibromin, a negative regulator of <jats:styled-content style=\"fixed-case\">RAS<\/jats:styled-content> activity. Mutation analysis of <jats:italic><jats:styled-content style=\"fixed-case\">NF<\/jats:styled-content>1<\/jats:italic> located at 17q11.2 has been hampered by the large size of the gene, the high rate of new mutations, the lack of mutational clustering, and the presence of several homologous loci. To date, about 80% of the reported <jats:italic><jats:styled-content style=\"fixed-case\">NF<\/jats:styled-content>1<\/jats:italic> mutations are predicted to result in protein truncation, but very few studies have correlated the causative <jats:italic><jats:styled-content style=\"fixed-case\">NF<\/jats:styled-content>1<\/jats:italic> mutation with its effect at the protein level. We evaluated a novel diagnostic method to detect truncated forms of neurofibromin in a large cohort of unrelated subjects suspected of having <jats:styled-content style=\"fixed-case\">NF<\/jats:styled-content>1, according to the <jats:styled-content style=\"fixed-case\">NIH<\/jats:styled-content> consensus criteria. Western blot analysis was carried out on protein extracts from patients' leukocytes to highlight the possible presence of altered neurofibromin as a result of mutations in <jats:italic><jats:styled-content style=\"fixed-case\">NF<\/jats:styled-content>1<\/jats:italic>. Truncated neurofibromin was identified in 274\/336 patients (81%), confirming the usefulness and reproducibility of the proposed diagnostic approach. Our methodology can be routinely applied in the diagnostic setting, thanks to its simplicity and reliability. Combined with molecular approaches, it may increase the accuracy and efficiency of <jats:italic><jats:styled-content style=\"fixed-case\">NF<\/jats:styled-content>1<\/jats:italic> genetic testing.<\/jats:p><\/jats:sec><jats:sec><jats:label\/><jats:p>\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc13396-fig-0004-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text>\nWe evaluated a novel diagnostic method to detect truncated forms of neurofibromin in patients fulfilling the clinical criteria for Neurofibromatosis 1. Western blot analysis identified truncated neurofibromin in 274\/336 patients (81%). Our results indicate that the proposed technique is cheap and reliable, and could ideally be performed as a preliminary biochemical screening before molecular analysis of the NF1 gene.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jnc.13396","type":"journal-article","created":{"date-parts":[[2015,10,19]],"date-time":"2015-10-19T14:14:56Z","timestamp":1445264096000},"page":"1123-1128","source":"Crossref","is-referenced-by-count":14,"title":["A novel diagnostic method to detect truncated neurofibromin in neurofibromatosis 1"],"prefix":"10.1111","volume":"135","author":[{"given":"Teresa","family":"Esposito","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Genetics Department of Experimental Medicine section F.Bottazzi Second University of Naples Naples Italy"},{"name":"Services Dietetics Department of Experimental Medicine section F.Bottazzi Second University of Naples Naples Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giulio","family":"Piluso","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Biophysics and General Pathology Second University of Naples Naples Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dario","family":"Saracino","sequence":"additional","affiliation":[{"name":"Division of Neurology &amp; InterUniversity Center for Research in Neuroscience Department of Clinical and Experimental Medicine and Surgery Second University of Naples Naples Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rossella","family":"Uccello","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Genetics Department of Experimental Medicine section F.Bottazzi Second University of Naples Naples Italy"},{"name":"Division of Neurology &amp; InterUniversity Center for Research in Neuroscience Department of Clinical and Experimental Medicine and Surgery Second University of Naples Naples Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carla","family":"Schettino","sequence":"additional","affiliation":[{"name":"Division of Neurology &amp; InterUniversity Center for Research in Neuroscience Department of Clinical and Experimental Medicine and Surgery Second University of Naples Naples Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clemente","family":"Dato","sequence":"additional","affiliation":[{"name":"Division of Neurology &amp; InterUniversity Center for Research in Neuroscience Department of Clinical and Experimental Medicine and Surgery Second University of Naples Naples Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guglielmo","family":"Capaldo","sequence":"additional","affiliation":[{"name":"Division of Neurology &amp; InterUniversity Center for Research in Neuroscience Department of Clinical and Experimental Medicine and Surgery Second University of Naples Naples Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Teresa","family":"Giugliano","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Biophysics and General Pathology Second University of Naples Naples Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bruno","family":"Varriale","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Genetics Department of Experimental Medicine section F.Bottazzi Second University of Naples Naples Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giuseppe","family":"Paolisso","sequence":"additional","affiliation":[{"name":"Department of Scienze Mediche, Chirurgiche, Neurologiche, Metaboliche e dell'Invecchiamento Second University of Naples Naples Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giuseppe","family":"Di Iorio","sequence":"additional","affiliation":[{"name":"Division of Neurology &amp; InterUniversity Center for Research in Neuroscience Department of Clinical and Experimental Medicine and Surgery Second University of Naples Naples Italy"},{"name":"Department of Scienze Mediche, Chirurgiche, Neurologiche, Metaboliche e dell'Invecchiamento Second University of Naples Naples Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariarosa A. B.","family":"Melone","sequence":"additional","affiliation":[{"name":"Division of Neurology &amp; InterUniversity Center for Research in Neuroscience Department of Clinical and Experimental Medicine and Surgery Second University of Naples Naples Italy"},{"name":"Institute of Biosciences and Bioresources CNR (IBBR\u2010CNR) Naples Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2015,11,12]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/9.2.237"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.40.6.e82"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00208923"},{"key":"e_1_2_7_5_1","first-page":"135","article-title":"Giant thrombosed intracavernous carotid artery aneurysm presenting as Tolosa\u2010Hunt syndrome in a patient harboring a new pathogenic neurofibromatosis type 1 mutation: a case report and review of the literature","volume":"10","author":"Conforti R.","year":"2014","journal-title":"Neuropsychiatr. 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