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 |
|---|---|
| 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
Cite this
}
C9orf72 hexanucleotide repeat length in older population: normal variation and effects on cognition. / Kaivola, Karri; Kiviharju, Anna; Jansson, Lilja; Rantalainen, Ville; Eriksson, Johan G.; Strandberg, Timo E.; Laaksovirta, Hannu; Renton, Alan E; Traynor, Bryan J.; Myllykangas, Liisa; Tienari, Pentti.
In: Neurobiology of Aging, Vol. 84, 12.2019, p. 242.e7-242.e12.Research output: Contribution to journal › Article › Scientific › peer-review
TY - JOUR
T1 - C9orf72 hexanucleotide repeat length in older population: normal variation and effects on cognition
AU - Kaivola, Karri
AU - Kiviharju, Anna
AU - Jansson, Lilja
AU - Rantalainen, Ville
AU - Eriksson, Johan G.
AU - Strandberg, Timo E.
AU - Laaksovirta, Hannu
AU - Renton, Alan E
AU - Traynor, Bryan J.
AU - Myllykangas, Liisa
AU - Tienari, Pentti
PY - 2019/12
Y1 - 2019/12
N2 - 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.
AB - 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.
KW - 3124 Neurology and psychiatry
KW - Genetics
KW - Alzheimer's disease
KW - Dementia
KW - C9orf72
KW - Cohort studies
KW - HUNTINGTONS-DISEASE
KW - ALZHEIMERS-DISEASE
KW - EXPANSION
KW - SIZE
KW - ASSOCIATION
KW - DEMENTIA
KW - CHILDREN
KW - GROWTH
KW - BIRTH
KW - AGE
U2 - 10.1016/j.neurobiolaging.2019.02.026
DO - 10.1016/j.neurobiolaging.2019.02.026
M3 - Article
VL - 84
SP - 242.e7-242.e12
JO - Neurobiology of Aging
JF - Neurobiology of Aging
SN - 0197-4580
ER -