Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
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
_version_ 1783519162149109760
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
work_keys_str_mv AT dardisandrea moleculargeneticsofniemannpicktypecdiseaseinitalyanupdateon105patientsanddescriptionof18npc1novelvariants
AT zampieristefania moleculargeneticsofniemannpicktypecdiseaseinitalyanupdateon105patientsanddescriptionof18npc1novelvariants
AT gelleracinzia moleculargeneticsofniemannpicktypecdiseaseinitalyanupdateon105patientsanddescriptionof18npc1novelvariants
AT carrozzorosalba moleculargeneticsofniemannpicktypecdiseaseinitalyanupdateon105patientsanddescriptionof18npc1novelvariants
AT cattarossisilvia moleculargeneticsofniemannpicktypecdiseaseinitalyanupdateon105patientsanddescriptionof18npc1novelvariants
AT peruzzopaolo moleculargeneticsofniemannpicktypecdiseaseinitalyanupdateon105patientsanddescriptionof18npc1novelvariants
AT dariolrosalia moleculargeneticsofniemannpicktypecdiseaseinitalyanupdateon105patientsanddescriptionof18npc1novelvariants
AT sechiannalisa moleculargeneticsofniemannpicktypecdiseaseinitalyanupdateon105patientsanddescriptionof18npc1novelvariants
AT deodatofederica moleculargeneticsofniemannpicktypecdiseaseinitalyanupdateon105patientsanddescriptionof18npc1novelvariants
AT cacciaclaudio moleculargeneticsofniemannpicktypecdiseaseinitalyanupdateon105patientsanddescriptionof18npc1novelvariants
AT verrignidaniela moleculargeneticsofniemannpicktypecdiseaseinitalyanupdateon105patientsanddescriptionof18npc1novelvariants
AT gasperiniserena moleculargeneticsofniemannpicktypecdiseaseinitalyanupdateon105patientsanddescriptionof18npc1novelvariants
AT fiumaraagata moleculargeneticsofniemannpicktypecdiseaseinitalyanupdateon105patientsanddescriptionof18npc1novelvariants
AT fecarottasimona moleculargeneticsofniemannpicktypecdiseaseinitalyanupdateon105patientsanddescriptionof18npc1novelvariants
AT carecchiomiryam moleculargeneticsofniemannpicktypecdiseaseinitalyanupdateon105patientsanddescriptionof18npc1novelvariants
AT filostomassimiliano moleculargeneticsofniemannpicktypecdiseaseinitalyanupdateon105patientsanddescriptionof18npc1novelvariants
AT santorolucia moleculargeneticsofniemannpicktypecdiseaseinitalyanupdateon105patientsanddescriptionof18npc1novelvariants
AT borronibarbara moleculargeneticsofniemannpicktypecdiseaseinitalyanupdateon105patientsanddescriptionof18npc1novelvariants
AT bordugoandrea moleculargeneticsofniemannpicktypecdiseaseinitalyanupdateon105patientsanddescriptionof18npc1novelvariants
AT brancatifrancesco moleculargeneticsofniemannpicktypecdiseaseinitalyanupdateon105patientsanddescriptionof18npc1novelvariants
AT russocinziav moleculargeneticsofniemannpicktypecdiseaseinitalyanupdateon105patientsanddescriptionof18npc1novelvariants
AT diroccomaja moleculargeneticsofniemannpicktypecdiseaseinitalyanupdateon105patientsanddescriptionof18npc1novelvariants
AT toscanoantonio moleculargeneticsofniemannpicktypecdiseaseinitalyanupdateon105patientsanddescriptionof18npc1novelvariants
AT scarpamaurizio moleculargeneticsofniemannpicktypecdiseaseinitalyanupdateon105patientsanddescriptionof18npc1novelvariants
AT bembibruno moleculargeneticsofniemannpicktypecdiseaseinitalyanupdateon105patientsanddescriptionof18npc1novelvariants