Abstract
The hexanucleotide repeat expansion in C9orf72 is a common cause of amyotrophic lateral sclerosis/frontotemporal dementia and also rarely found in other psychiatric and neurodegenerative conditions. Alleles with >30 repeats are often considered an expansion, but the pathogenic repeat length threshold is still unclear. It is also unclear whether intermediate repeat length alleles (often defined either as 7-30 or 20-30 repeats) have clinically significant effects. We determined the C9orf72 repeat length distribution in 3142 older Finns (aged 60-104 years). The longest nonexpanded allele was 45 repeats. We found 7-45 repeats in 1036/3142 (33%) individuals, 20-45 repeats in 56/3142 (1.8%), 30-45 repeats in 12/3142 (0.38%), and expansion (>45 repeats) in 6/3142 (0.19%). There was no apparent clustering of neurodegenerative or psychiatric diseases in individuals with 30-45 repeats indicating that 30-45 repeats are not pathogenic. None of the 6 expansion carriers had a diagnosis of amyotrophic lateral sclerosis/frontotemporal dementia but 4 had a diagnosis of a neurodegenerative or psychiatric disease. Intermediate length alleles (categorized as 7-45 and 20-45 repeats) did not associate with Alzheimer's disease or cognitive impairment. (C) 2019 The Author(s). Published by Elsevier Inc.
Original language | English |
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Journal | Neurobiology of Aging |
Volume | 84 |
Pages (from-to) | 242.e7-242.e12 |
Number of pages | 6 |
ISSN | 0197-4580 |
DOIs | |
Publication status | Published - Dec 2019 |
MoE publication type | A1 Journal article-refereed |
Fields of Science
- 3124 Neurology and psychiatry
- Genetics
- Alzheimer's disease
- Dementia
- C9orf72
- Cohort studies
- HUNTINGTONS-DISEASE
- ALZHEIMERS-DISEASE
- EXPANSION
- SIZE
- ASSOCIATION
- DEMENTIA
- CHILDREN
- GROWTH
- BIRTH
- AGE