Karri Kaivola, Anna Kiviharju, Lilja Jansson, Ville Rantalainen, Johan G. Eriksson, Timo E. Strandberg, Hannu Laaksovirta, Alan E. Renton, Bryan J. Traynor, Liisa Myllykangas, Pentti J. Tienari, C9orf72 hexanucleotide repeat length in older population: normal variation and effects on cognition, Neurobiology of Aging, Volume 84, 2019, Pages 242.e7-242.e12, ISSN 0197-4580, https://doi.org/10.1016/j.neurobiolaging.2019.02.026
C9orf72 hexanucleotide repeat length in older population : normal variation and effects on cognition
|Author:||Kaivola, Karri1; Kiviharju, Anna1; Jansson, Lilja1;|
1Molecular Neurology, Research Programs Unit, Department of Neurology, University of Helsinki, Helsinki University Hospital, Helsinki, Finland
2Department of Psychology and Logopedics, University of Helsinki, Helsinki, Finland
3Folkhälsan Research Center, Helsinki, Finland
4Department of General Practice and Primary Health Care, University of Helsinki, Helsinki University Hospital, Unit of General Practice, Helsinki, Finland
5Department of General Practice and Primary Health Care, National Institute for Health and Welfare, Helsinki, Finland
6Centre for Life Course Health Research, University of Oulu, Oulu, Finland
7University of Helsinki, Helsinki University Hospital, Helsinki, Finland
8Department of Neuroscience, Ronald M. Loeb Center for Alzheimer's Disease, Icahn School of Medicine at Mount Sinai, New York, NY, USA
9Laboratory of Neurogenetics, National Institutes on Aging, NIH, Bethesda, MD, USA
10Department of Pathology, University of Helsinki and HUSLAB, Helsinki University Hospital, Helsinki, Finland
|Online Access:||PDF Full Text (PDF, 0.4 MB)|
|Persistent link:|| http://urn.fi/urn:nbn:fi-fe202002104962
|Publish Date:|| 2020-02-10
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.
Neurobiology of aging
|Pages:||242.e7 - 242.e12|
|Type of Publication:||
A1 Journal article – refereed
|Field of Science:||
3121 General medicine, internal medicine and other clinical medicine
KK was funded by the Finnish Cultural Foundation and the UH Faculty of Medicine MD/PhD program. PJT has been supported by grants from the Sigrid Juselius Foundation and Helsinki University Hospital. This work was funded in part by the Intramural Research Program of the National Institute on Aging, National Institutes of Health (Z01-AG000949). LM has received funding from the Academy of Finland (grant number 294817).
The Helsinki Birth cohort study has been funded by The Academy of Finland, the Finnish Diabetes Research society, Folkhälsan Research Foundation, Novo Nordisk Foundation, Finska Läkaresällskapet, Signe and Ane Gyllenberg Foundation, University of Helsinki, Ahokas Foundation, Juho Vainio Foundation, and Helsinki University Hospital.
The Helsinki Businessmen study has been funded by VTR-funding of the HUS/Helsinki University Hospital (TYH 2014245; 2015211, Sisu) and the Academy of Finland (grant number 311492). The authors are grateful to Professor Simon Mead (National Prion Clinic, MRC Prion Unit at the University College London) for sharing detailed C9orf72 allele distribution in the UK 1958 birth cohort.
© 2019 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).