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Genetic screening for Niemann–Pick disease type C in adults with neurological and psychiatric symptoms: findings from the ZOOM study

Niemann–Pick disease type C (NP-C) is a rare, autosomal-recessive, progressive neurological disease caused by mutations in either the NPC1 gene (in 95% of cases) or the NPC2 gene. This observational, multicentre genetic screening study evaluated the frequency and phenotypes of NP-C in consecutive ad...

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Autores principales: Bauer, Peter, Balding, David J., Klünemann, Hans H., Linden, David E. J., Ory, Daniel S., Pineda, Mercè, Priller, Josef, Sedel, Frederic, Muller, Audrey, Chadha-Boreham, Harbajan, Welford, Richard W. D., Strasser, Daniel S., Patterson, Marc C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3792693/
https://www.ncbi.nlm.nih.gov/pubmed/23773996
http://dx.doi.org/10.1093/hmg/ddt284
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author Bauer, Peter
Balding, David J.
Klünemann, Hans H.
Linden, David E. J.
Ory, Daniel S.
Pineda, Mercè
Priller, Josef
Sedel, Frederic
Muller, Audrey
Chadha-Boreham, Harbajan
Welford, Richard W. D.
Strasser, Daniel S.
Patterson, Marc C.
author_facet Bauer, Peter
Balding, David J.
Klünemann, Hans H.
Linden, David E. J.
Ory, Daniel S.
Pineda, Mercè
Priller, Josef
Sedel, Frederic
Muller, Audrey
Chadha-Boreham, Harbajan
Welford, Richard W. D.
Strasser, Daniel S.
Patterson, Marc C.
author_sort Bauer, Peter
collection PubMed
description Niemann–Pick disease type C (NP-C) is a rare, autosomal-recessive, progressive neurological disease caused by mutations in either the NPC1 gene (in 95% of cases) or the NPC2 gene. This observational, multicentre genetic screening study evaluated the frequency and phenotypes of NP-C in consecutive adult patients with neurological and psychiatric symptoms. Diagnostic testing for NP-C involved NPC1 and NPC2 exonic gene sequencing and gene dosage analysis. When available, results of filipin staining, plasma cholestane-3β,5α,6β-triol assays and measurements of relevant sphingolipids were also collected. NPC1 and NPC2 gene sequencing was completed in 250/256 patients from 30 psychiatric and neurological reference centres across the EU and USA [median (range) age 38 (18–90) years]. Three patients had a confirmed diagnosis of NP-C; two based on gene sequencing alone (two known causal disease alleles) and one based on gene sequencing and positive filipin staining. A further 12 patients displayed either single mutant NP-C alleles (8 with NPC1 mutations and 3 with NPC2 mutations) or a known causal disease mutation and an unclassified NPC1 allele variant (1 patient). Notably, high plasma cholestane-3β,5α,6β-triol levels were observed for all NP-C cases (n = 3). Overall, the frequency of NP-C patients in this study [1.2% (95% CI; 0.3%, 3.5%)] suggests that there may be an underdiagnosed pool of NP-C patients among adults who share common neurological and psychiatric symptoms.
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spelling pubmed-37926932013-10-18 Genetic screening for Niemann–Pick disease type C in adults with neurological and psychiatric symptoms: findings from the ZOOM study Bauer, Peter Balding, David J. Klünemann, Hans H. Linden, David E. J. Ory, Daniel S. Pineda, Mercè Priller, Josef Sedel, Frederic Muller, Audrey Chadha-Boreham, Harbajan Welford, Richard W. D. Strasser, Daniel S. Patterson, Marc C. Hum Mol Genet Articles Niemann–Pick disease type C (NP-C) is a rare, autosomal-recessive, progressive neurological disease caused by mutations in either the NPC1 gene (in 95% of cases) or the NPC2 gene. This observational, multicentre genetic screening study evaluated the frequency and phenotypes of NP-C in consecutive adult patients with neurological and psychiatric symptoms. Diagnostic testing for NP-C involved NPC1 and NPC2 exonic gene sequencing and gene dosage analysis. When available, results of filipin staining, plasma cholestane-3β,5α,6β-triol assays and measurements of relevant sphingolipids were also collected. NPC1 and NPC2 gene sequencing was completed in 250/256 patients from 30 psychiatric and neurological reference centres across the EU and USA [median (range) age 38 (18–90) years]. Three patients had a confirmed diagnosis of NP-C; two based on gene sequencing alone (two known causal disease alleles) and one based on gene sequencing and positive filipin staining. A further 12 patients displayed either single mutant NP-C alleles (8 with NPC1 mutations and 3 with NPC2 mutations) or a known causal disease mutation and an unclassified NPC1 allele variant (1 patient). Notably, high plasma cholestane-3β,5α,6β-triol levels were observed for all NP-C cases (n = 3). Overall, the frequency of NP-C patients in this study [1.2% (95% CI; 0.3%, 3.5%)] suggests that there may be an underdiagnosed pool of NP-C patients among adults who share common neurological and psychiatric symptoms. Oxford University Press 2013-11-01 2013-06-16 /pmc/articles/PMC3792693/ /pubmed/23773996 http://dx.doi.org/10.1093/hmg/ddt284 Text en © The Author 2013. Published by Oxford University Press. http://creativecommons.org/licenses/by/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Articles
Bauer, Peter
Balding, David J.
Klünemann, Hans H.
Linden, David E. J.
Ory, Daniel S.
Pineda, Mercè
Priller, Josef
Sedel, Frederic
Muller, Audrey
Chadha-Boreham, Harbajan
Welford, Richard W. D.
Strasser, Daniel S.
Patterson, Marc C.
Genetic screening for Niemann–Pick disease type C in adults with neurological and psychiatric symptoms: findings from the ZOOM study
title Genetic screening for Niemann–Pick disease type C in adults with neurological and psychiatric symptoms: findings from the ZOOM study
title_full Genetic screening for Niemann–Pick disease type C in adults with neurological and psychiatric symptoms: findings from the ZOOM study
title_fullStr Genetic screening for Niemann–Pick disease type C in adults with neurological and psychiatric symptoms: findings from the ZOOM study
title_full_unstemmed Genetic screening for Niemann–Pick disease type C in adults with neurological and psychiatric symptoms: findings from the ZOOM study
title_short Genetic screening for Niemann–Pick disease type C in adults with neurological and psychiatric symptoms: findings from the ZOOM study
title_sort genetic screening for niemann–pick disease type c in adults with neurological and psychiatric symptoms: findings from the zoom study
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3792693/
https://www.ncbi.nlm.nih.gov/pubmed/23773996
http://dx.doi.org/10.1093/hmg/ddt284
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