Octapeptide repeat insertions in the prion protein gene and early onset dementia
| Autor: | C. Van Broeckhoven, Bart Dermaut, J. Theuns, Esther A. Croes, M Van den Broeck, Jeanine J. Houwing-Duistermaat, K. Sleegers, J. C. van Swieten, Gerwin Roks, Marc Cruts, C M van Duijn, B van Harten |
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| Přispěvatelé: | Epidemiology, Neurology |
| Rok vydání: | 2004 |
| Předmět: |
Time Factors
Prions animal diseases Short Report medicine.disease_cause Presenilin PRNP mental disorders medicine PSEN1 Amyloid precursor protein Humans Dementia Age of Onset Repetitive Sequences Nucleic Acid Fatal familial insomnia Genetics Mutation biology medicine.disease nervous system diseases Psychiatry and Mental health Phenotype Disease Progression biology.protein Regression Analysis Surgery Neurology (clinical) Age of onset |
| Zdroj: | Journal of Neurology Neurosurgery and Psychiatry, 75, 1166-1170. BMJ Publishing Group Journal of neurology, neurosurgery and psychiatry |
| ISSN: | 0022-3050 |
| DOI: | 10.1136/jnnp.2003.020198 |
| Popis: | Objectives: The most common familial early onset dementia mutations are found in the genes involved in Alzheimer’s disease; the amyloid precursor protein (APP) and the presenilin 1 and 2 (PSEN1 and 2) genes; the prion protein gene (PRNP) may be involved. Methods: Following identification of a two-octapeptide repeat insertion in PRNP, we conducted a meta-analysis to investigate the relation of number of PRNP octapeptide repeats with age at disease onset and duration of illness; identifying 55 patients with PRNP octapeptide repeat insertions. We used a linear mixed effects model to assess the relation of number of repeats with age at disease onset, and studied the effect of the number of inserted octapeptide repeats on disease duration with a Cox proportional hazards regression analysis. Results: We found an increasing number of repeats associated with younger age at onset (p,0.001). Duration of the disease decreased significantly with the length of the octapeptide repeat (p,0.001) when adjusting for age at onset. Conclusions: Our findings show significant inverse associations of the length of the PRNP octapeptide repeat with age at disease onset and disease duration in the spongiform encephalopathies. S everal genes are known in familial early onset dementias. The most common mutations are found in the genes involved in Alzheimer’s disease. This concerns mutations in the amyloid precursor protein (APP) and the presenilin 1 and 2 (PSEN1 and 2) genes. Further, mutations in the prion protein gene (PRNP) may be common in early onset dementia. 1 Mutations in PRNP may lead to different clinical phenotypes, including familial Creutzfeldt–Jakob ..... |
| Databáze: | OpenAIRE |
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