The C9orf72 repeat size correlates with onset age of disease, DNA methylation and transcriptional downregulation of the promoter

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:
0301 basic medicine
Epigenomics
Male
FEATURES
FRAGILE X-SYNDROME
AMYOTROPHIC-LATERAL-SCLEROSIS
Epigenesis
Genetic
0302 clinical medicine
Belgium
CLINICAL CHARACTERISTICS
C9orf72
methods [Epigenomics]
Medicine and Health Sciences
CPG-ISLAND
genetics [Genetic Predisposition to Disease]
Age of Onset
Promoter Regions
Genetic
Genetics
Medicine(all)
genetics [Epigenesis
Genetic]
DNA methylation
metabolism [Proteins]
Methylation
Middle Aged
genetics [Amyotrophic Lateral Sclerosis]
Psychiatry and Mental health
Chemistry
CpG site
FRIEDREICH ATAXIA
Female
Original Article
genetics [Frontotemporal Lobar Degeneration]
Adult
medicine.medical_specialty
PATHOLOGICAL
Down-Regulation
genetics [DNA Methylation]
03 medical and health sciences
Cellular and Molecular Neuroscience
Internal medicine
medicine
Humans
Genetic Predisposition to Disease
ddc:610
Molecular Biology
Biology
GGGGCC
FRONTOTEMPORAL LOBAR DEGENERATION
HEXANUCLEOTIDE REPEAT
C9orf72 Protein
business.industry
metabolism [Amyotrophic Lateral Sclerosis]
Amyotrophic Lateral Sclerosis
Proteins
Biology and Life Sciences
genetics [Proteins]
metabolism [Frontotemporal Lobar Degeneration]
030104 developmental biology
Endocrinology
genetics [Promoter Regions
Genetic]
RNA FOCI
Anticipation (genetics)
CpG Islands
Human medicine
C9orf72 protein
human
Age of onset
Frontotemporal Lobar Degeneration
NEURODEGENERATIVE DISORDERS
Trinucleotide repeat expansion
business
genetics [CpG Islands]
030217 neurology & neurosurgery
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
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