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Molecular Genetics of Niemann–Pick Type C Disease in Italy: An Update on 105 Patients and Description of 18 NPC1 Novel Variants
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 belo...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7141276/ https://www.ncbi.nlm.nih.gov/pubmed/32138288 http://dx.doi.org/10.3390/jcm9030679 |
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author | Dardis, Andrea Zampieri, Stefania Gellera, Cinzia Carrozzo, Rosalba Cattarossi, Silvia Peruzzo, Paolo Dariol, Rosalia Sechi, Annalisa Deodato, Federica Caccia, Claudio Verrigni, Daniela Gasperini, Serena Fiumara, Agata Fecarotta, Simona Carecchio, Miryam Filosto, Massimiliano Santoro, Lucia Borroni, Barbara Bordugo, Andrea Brancati, Francesco Russo, Cinzia V. Di Rocco, Maja Toscano, Antonio Scarpa, Maurizio Bembi, Bruno |
author_facet | Dardis, Andrea Zampieri, Stefania Gellera, Cinzia Carrozzo, Rosalba Cattarossi, Silvia Peruzzo, Paolo Dariol, Rosalia Sechi, Annalisa Deodato, Federica Caccia, Claudio Verrigni, Daniela Gasperini, Serena Fiumara, Agata Fecarotta, Simona Carecchio, Miryam Filosto, Massimiliano Santoro, Lucia Borroni, Barbara Bordugo, Andrea Brancati, Francesco Russo, Cinzia V. Di Rocco, Maja Toscano, Antonio Scarpa, Maurizio Bembi, Bruno |
author_sort | Dardis, Andrea |
collection | PubMed |
description | 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’s 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. |
format | Online Article Text |
id | pubmed-7141276 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-71412762020-04-10 Molecular Genetics of Niemann–Pick Type C Disease in Italy: An Update on 105 Patients and Description of 18 NPC1 Novel Variants Dardis, Andrea Zampieri, Stefania Gellera, Cinzia Carrozzo, Rosalba Cattarossi, Silvia Peruzzo, Paolo Dariol, Rosalia Sechi, Annalisa Deodato, Federica Caccia, Claudio Verrigni, Daniela Gasperini, Serena Fiumara, Agata Fecarotta, Simona Carecchio, Miryam Filosto, Massimiliano Santoro, Lucia Borroni, Barbara Bordugo, Andrea Brancati, Francesco Russo, Cinzia V. Di Rocco, Maja Toscano, Antonio Scarpa, Maurizio Bembi, Bruno J Clin Med Article 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’s 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. MDPI 2020-03-03 /pmc/articles/PMC7141276/ /pubmed/32138288 http://dx.doi.org/10.3390/jcm9030679 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Dardis, Andrea Zampieri, Stefania Gellera, Cinzia Carrozzo, Rosalba Cattarossi, Silvia Peruzzo, Paolo Dariol, Rosalia Sechi, Annalisa Deodato, Federica Caccia, Claudio Verrigni, Daniela Gasperini, Serena Fiumara, Agata Fecarotta, Simona Carecchio, Miryam Filosto, Massimiliano Santoro, Lucia Borroni, Barbara Bordugo, Andrea Brancati, Francesco Russo, Cinzia V. Di Rocco, Maja Toscano, Antonio Scarpa, Maurizio Bembi, Bruno Molecular Genetics of Niemann–Pick Type C Disease in Italy: An Update on 105 Patients and Description of 18 NPC1 Novel Variants |
title | Molecular Genetics of Niemann–Pick Type C Disease in Italy: An Update on 105 Patients and Description of 18 NPC1 Novel Variants |
title_full | Molecular Genetics of Niemann–Pick Type C Disease in Italy: An Update on 105 Patients and Description of 18 NPC1 Novel Variants |
title_fullStr | Molecular Genetics of Niemann–Pick Type C Disease in Italy: An Update on 105 Patients and Description of 18 NPC1 Novel Variants |
title_full_unstemmed | Molecular Genetics of Niemann–Pick Type C Disease in Italy: An Update on 105 Patients and Description of 18 NPC1 Novel Variants |
title_short | Molecular Genetics of Niemann–Pick Type C Disease in Italy: An Update on 105 Patients and Description of 18 NPC1 Novel Variants |
title_sort | molecular genetics of niemann–pick type c disease in italy: an update on 105 patients and description of 18 npc1 novel variants |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7141276/ https://www.ncbi.nlm.nih.gov/pubmed/32138288 http://dx.doi.org/10.3390/jcm9030679 |
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