Autor: |
Gijselinck, I, Van Mossevelde, S, van der Zee, J, Sieben, Anne, Engelborghs, S, De Bleecker, Jan, Ivanoiu, A, Deryck, O, Edbauer, D, Zhang, M, Heeman, B, Baumer, V, Van den Broeck, M, Mattheijssens, M, Peeters, K, Rogaeva, E, De Jonghe, P, Cras, P, Martin, J-J, de Deyn, PP, Cruts, M, Van Broeckhoven, C, BELNEU consortium, the, Dermaut, Bart, Santens, Patrick, Van Langenhove, Tim |
Přispěvatelé: |
Clinical sciences, Neuroprotection & Neuromodulation, Neurology, BELNEU Consortium, UCL - SSS/IONS/NEUR - Clinical Neuroscience, UCL - (SLuc) Service de neurologie |
Jazyk: |
angličtina |
Rok vydání: |
2016 |
Předmět: |
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Zdroj: |
MOLECULAR PSYCHIATRY Molecular Psychiatry Molecular psychiatry Molecular psychiatry 21(8), 1112-1124 (2015). doi:10.1038/mp.2015.159 Molecular Psychiatry, Vol. 21, no. 8, p. 1112-1124 (2016) |
ISSN: |
1359-4184 1476-5578 |
Popis: |
Pathological expansion of a G(4)C(2) repeat, located in the 5' regulatory region of C9orf72, is the most common genetic cause of frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). C9orf72 patients have highly variable onset ages suggesting the presence of modifying factors and/or anticipation. We studied 72 Belgian index patients with FTLD, FTLD-ALS or ALS and 61 relatives with a C9orf72 repeat expansion. We assessed the effect of G(4)C(2) expansion size on onset age, the role of anticipation and the effect of repeat size on methylation and C9orf72 promoter activity. G(4)C(2) expansion sizes varied in blood between 45 and over 2100 repeat units with short expansions (45-78 units) present in 5.6% of 72 index patients with an expansion. Short expansions co-segregated with disease in two families. The subject with a short expansion in blood but an indication of mosaicism in brain showed the same pathology as those with a long expansion. Further, we provided evidence for an association of G(4)C(2) expansion size with onset age (P |
Databáze: |
OpenAIRE |
Externí odkaz: |
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