Zech, Michael and Nuebling, Georg and Castrop, Florian and Jochim, Angela and Schulte, Eva C. and Mollenhauer, Brit and Lichtner, Peter and Peters, Annette and Gieger, Christian and Marquardt, Thorsten and Vanier, Marie T. and Latour, Philippe and Kluenemann, Hans and Trenkwalder, Claudia and Diehlschmid, Janine and Perneczky, Robert and Meitinger, Thomas and Oexle, Konrad and Haslinger, Bernhard and Lorenzl, Stefan and Winkelmann, Juliane (2013) Niemann-Pick C Disease Gene Mutations and Age-Related Neurodegenerative Disorders. PLOS ONE, 8 (12): e82879. ISSN 1932-6203,
Full text not available from this repository. (Request a copy)Abstract
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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | FRONTOTEMPORAL LOBAR DEGENERATION; PROGRESSIVE SUPRANUCLEAR PALSY; PARKINSONS-DISEASE; GLUCOCEREBROSIDASE MUTATIONS; MISSENSE MUTATIONS; NPC1 MUTATIONS; RISK-FACTOR; DIAGNOSIS; TRAFFICKING; IDENTIFICATION; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Psychiatrie und Psychotherapie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 23 Mar 2020 07:46 |
| Last Modified: | 23 Mar 2020 07:46 |
| URI: | https://pred.uni-regensburg.de/id/eprint/15504 |
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