{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T18:50:38Z","timestamp":1792263038527,"version":"4.4.0"},"reference-count":49,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2020,3,3]],"date-time":"2020-03-03T00:00:00Z","timestamp":1583193600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Niemann-Pick type C (NPC) disease is an autosomal recessive lysosomal storage disorder caused by mutations in NPC1 or NPC2 genes. In 2009, the molecular characterization of 44 NPC Italian patients has been published. Here, we present an update of the genetic findings in 105 Italian NPC patients belonging to 83 unrelated families (77 NPC1 and 6 NPC2). NPC1 and NPC2 genes were studied following an algorithm recently published. Eighty-four different NPC1 and five NPC2 alleles were identified. Only two NPC1 alleles remained non detected. Sixty-two percent of NPC1 alleles were due to missense variants. The most frequent NPC1 mutation was the p.F284Lfs*26 (5.8% of the alleles). All NPC2 mutations were found in the homozygous state, and all but one was severe. Among newly diagnosed patients, 18 novel NPC1 mutations were identified. The pathogenic nature of 7\/9 missense alleles and 3\/4 intronic variants was confirmed by filipin staining and NPC1 protein analysis or mRNA expression in patient\u2019s fibroblasts. Taken together, our previous published data and new results provide an overall picture of the molecular characteristics of NPC patients diagnosed so far in Italy.<\/jats:p>","DOI":"10.3390\/jcm9030679","type":"journal-article","created":{"date-parts":[[2020,3,3]],"date-time":"2020-03-03T13:06:23Z","timestamp":1583240783000},"page":"679","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Molecular Genetics of Niemann\u2013Pick Type C Disease in Italy: An Update on 105 Patients and Description of 18 NPC1 Novel Variants"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7024-8181","authenticated-orcid":false,"given":"Andrea","family":"Dardis","sequence":"first","affiliation":[{"name":"Regional Coordinator Centre for Rare Diseases, University Hospital of Udine, 33100 Udine, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefania","family":"Zampieri","sequence":"additional","affiliation":[{"name":"Regional Coordinator Centre for Rare Diseases, University Hospital of Udine, 33100 Udine, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cinzia","family":"Gellera","sequence":"additional","affiliation":[{"name":"Unit of Genetics of Neurodegenerative and Metabolic Diseases Fondazione IRCCS Istituto Neurologico Carlo Besta, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosalba","family":"Carrozzo","sequence":"additional","affiliation":[{"name":"Unit of Muscular and Neurodegenerative Disorders, Laboratory of Molecular Medicine, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, 00146 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Cattarossi","sequence":"additional","affiliation":[{"name":"Regional Coordinator Centre for Rare Diseases, University Hospital of Udine, 33100 Udine, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Peruzzo","sequence":"additional","affiliation":[{"name":"Regional Coordinator Centre for Rare Diseases, University Hospital of Udine, 33100 Udine, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosalia","family":"Dariol","sequence":"additional","affiliation":[{"name":"Regional Coordinator Centre for Rare Diseases, University Hospital of Udine, 33100 Udine, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annalisa","family":"Sechi","sequence":"additional","affiliation":[{"name":"Regional Coordinator Centre for Rare Diseases, University Hospital of Udine, 33100 Udine, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Deodato","sequence":"additional","affiliation":[{"name":"Division of Metabolism, Departement of Pediatric Subspecialities, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, 00146 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudio","family":"Caccia","sequence":"additional","affiliation":[{"name":"Unit of Genetics of Neurodegenerative and Metabolic Diseases Fondazione IRCCS Istituto Neurologico Carlo Besta, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Verrigni","sequence":"additional","affiliation":[{"name":"Unit of Muscular and Neurodegenerative Disorders, Laboratory of Molecular Medicine, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, 00146 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serena","family":"Gasperini","sequence":"additional","affiliation":[{"name":"Pediatric Rare Diseases Unit, Department of Pediatrics, MBBM Foundation, ATS Monza e Brianza, 20900 Monza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agata","family":"Fiumara","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Regional Referral Center for Inherited Metabolic Disease, University of Catania, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona","family":"Fecarotta","sequence":"additional","affiliation":[{"name":"Department of Pediatrics \u201cFederico II\u201d University Hospital, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miryam","family":"Carecchio","sequence":"additional","affiliation":[{"name":"Unit of Genetics of Neurodegenerative and Metabolic Diseases Fondazione IRCCS Istituto Neurologico Carlo Besta, 20133 Milan, Italy"},{"name":"Department of Neuroscience, University of Padua, Via Giustiniani 2, 35128 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2852-7512","authenticated-orcid":false,"given":"Massimiliano","family":"Filosto","sequence":"additional","affiliation":[{"name":"Center for Neuromuscular Diseases, Unit of Neurology, ASST \u201cSpedali Civili\u201d and University of Brescia, 25123 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"Santoro","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, Division of Pediatrics, Polytechnic University of Marche, Ospedali Riuniti, 60020 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Borroni","sequence":"additional","affiliation":[{"name":"Centre for Neurodegenerative Disorders, Department of Clinical and Experimental Sciences, University of Brescia, 25123 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Bordugo","sequence":"additional","affiliation":[{"name":"Inherited Metabolic Disease Unit and Regional Centre for Newborn Screening, Children and Women Hospital, Azienda Ospedaliera Universit\u00e0 Integrata, 37126 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Brancati","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit, Tor Vergata University, 00133 Roma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cinzia V.","family":"Russo","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Reproductive and Odontostomatological Sciences, Federico II University, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maja","family":"Di Rocco","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Unit of Rare Diseases, Giannina Gaslini 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