PuSH - Publikationsserver des Helmholtz Zentrums München

Export: TXT Text RIS Endnote (RIS) BIB BibTeX
Zech, M. ; Nübling, G.* ; Castrop, F.* ; Jochim, A.* ; Schulte, E.C. ; Mollenhauer, B.* ; Lichtner, P. ; Peters, A. ; Gieger, C. ; Marquardt, T.* ; Vanier, M.T.* ; Latour, P.* ; Klünemann, H.H.* ; Trenkwalder, C.* ; Diehl-Schmid, J.* ; Perneczky, R.* ; Meitinger, T. ; Oexle, K. ; Haslinger, B.* ; Lorenzl, S.* ; Winkelmann, J.

Niemann-pick C disease gene mutations and age-related neurodegenerative disorders.

PLoS ONE 8:e82879 (2013)
Verlagsversion Volltext DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Niemann-Pick type C (NPC) disease is a rare autosomal-recessively inherited lysosomal storage disorder caused by mutations in NPC1 (95%) or NPC2. Given the highly variable phenotype, diagnosis is challenging and particularly late-onset forms with predominantly neuropsychiatric presentations are likely underdiagnosed. Pathophysiologically, genetic alterations compromising the endosomal/lysosomal system are linked with age-related neurodegenerative disorders. We sought to examine a possible association of rare sequence variants in NPC1 and NPC2 with Parkinson's disease (PD), frontotemporal lobar degeneration (FTLD) and progressive supranuclear palsy (PSP), and to genetically determine the proportion of potentially misdiagnosed NPC patients in these neurodegenerative conditions. By means of high-resolution melting, we screened the coding regions of NPC1 and NPC2 for rare genetic variation in a homogenous German sample of patients clinically diagnosed with PD (n = 563), FTLD (n = 133) and PSP (n = 94), and 846 population-based controls. The frequencies of rare sequence variants in NPC1/2 did not differ significantly between patients and controls. Disease-associated NPC1/2 mutations were found in six PD patients (1.1%) and seven control subjects (0.8%), but not in FTLD or PSP. All rare variation was detected in the heterozygous state and no compound heterozygotes were observed. Our data do not support the hypothesis that rare NPC1/2 variants confer susceptibility for PD, FTLD, or PSP in the German population. Misdiagnosed NPC patients were not present in our samples. However, further assessment of NPC disease genes in age-related neurodegeneration is warranted.
Impact Factor
Scopus SNIP
Web of Science
Times Cited
Scopus
Cited By
Altmetric
3.534
1.063
32
38
Tags
Anmerkungen
Besondere Publikation
Auf Hompepage verbergern

Zusatzinfos bearbeiten
Eigene Tags bearbeiten
Privat
Eigene Anmerkung bearbeiten
Privat
Auf Publikationslisten für
Homepage nicht anzeigen
Als besondere Publikation
markieren
Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Frontotemporal Lobar Degeneration; Progressive Supranuclear Palsy; Parkinsons-disease; Glucocerebrosidase Mutations; Missense Mutations; Npc1 Mutations; Risk-factor; Diagnosis; Trafficking; Identification
Sprache englisch
Veröffentlichungsjahr 2013
HGF-Berichtsjahr 2014
ISSN (print) / ISBN 1932-6203
Zeitschrift PLoS ONE
Quellenangaben Band: 8, Heft: 12, Seiten: , Artikelnummer: e82879 Supplement: ,
Verlag Public Library of Science (PLoS)
Verlagsort Lawrence, Kan.
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Human Genetics (IHG)
Institute of Epidemiology (EPI)
Institute of Genetic Epidemiology (IGE)
POF Topic(s) 30501 - Systemic Analysis of Genetic and Environmental Factors that Impact Health
30202 - Environmental Health
Forschungsfeld(er) Genetics and Epidemiology
PSP-Element(e) G-500700-001
G-504000-001
G-504100-001
PubMed ID 24386122
DOI 10.1371/journal.pone.0082879
WOS ID WOS:000329194700015
Scopus ID 84893673648
Erfassungsdatum 2014-01-30
[➜Korrektur melden]