PuSH - Publikationsserver des Helmholtz Zentrums München

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.
Altmetric
Weitere Metriken?
Zusatzinfos bearbeiten [➜Einloggen]
Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Frontotemporal Lobar Degeneration; Progressive Supranuclear Palsy; Parkinsons-disease; Glucocerebrosidase Mutations; Missense Mutations; Npc1 Mutations; Risk-factor; Diagnosis; Trafficking; Identification
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.
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed