C9orf72 hexanucleotide repeat length in older population: normal variation and effects on cognition
| Autor: | Anna Kiviharju, Pentti J. Tienari, Johan G. Eriksson, Ville Rantalainen, Timo E. Strandberg, Lilja Jansson, Alan E. Renton, Liisa Myllykangas, Hannu Laaksovirta, Karri Kaivola, Bryan J. Traynor |
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| Přispěvatelé: | Neurologian yksikkö, University of Helsinki, HUS Neurocenter, Research Programs Unit, Department of Psychology and Logopedics, Developmental Psychology Research Group, Clinicum, Department of General Practice and Primary Health Care, HUS Internal Medicine and Rehabilitation, Timo Strandberg / Principal Investigator, Department of Medicine, University Management, Department of Neurosciences, HUSLAB, Department of Pathology, Medicum |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Male Aging BIRTH CHILDREN Disease Biology 3124 Neurology and psychiatry Article Cohort Studies 03 medical and health sciences AGE 0302 clinical medicine Cognition C9orf72 Genetics medicine Dementia Humans Allele Amyotrophic lateral sclerosis Aged Aged 80 and over DNA Repeat Expansion C9orf72 Protein DEMENTIA General Neuroscience Amyotrophic Lateral Sclerosis EXPANSION ASSOCIATION Alzheimer's disease Middle Aged medicine.disease ALZHEIMERS-DISEASE SIZE 030104 developmental biology Frontotemporal Dementia HUNTINGTONS-DISEASE GROWTH Female Neurology (clinical) Geriatrics and Gerontology Trinucleotide repeat expansion 030217 neurology & neurosurgery Developmental Biology Frontotemporal dementia |
| Zdroj: | Neurobiol Aging |
| ISSN: | 1558-1497 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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