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 languageEnglish
JournalNeurobiology of Aging
Volume84
Pages (from-to)242.e7-242.e12
Number of pages6
ISSN0197-4580
DOIs
Publication statusPublished - Dec 2019
MoE publication typeA1 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

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