C9orf72 hexanucleotide repeat expansions as the causative mutation for chromosome 9p21-linked amyotrophic lateral sclerosis and frontotemporal dementia

Arch Neurol. 2012 Sep;69(9):1159-63. doi: 10.1001/archneurol.2012.377.

Abstract

Objective: To further assess the presence of a large hexanucleotide repeat expansion in the first intron of the C9orf72 gene identified as the genetic cause of chromosome 9p21-linked amyotrophic lateral sclerosis and frontotemporal dementia (c9ALS/FTD) in 4 unrelated families with a conclusive linkage to c9ALS/FTD.

Design: A repeat-primed polymerase chain reaction assay.

Setting: Academic research.

Participants: Affected and unaffected individuals from 4 ALS/FTD families.

Main outcome measure: The amplified C9orf72 repeat expansion.

Results: We show that the repeat is expanded in and segregated perfectly with the disease in these 4 pedigrees.

Conclusion: Our findings further confirm the C9orf72 hexanucleotide repeat expansion as the causative mutation for c9ALS/FTD and strengthen the hypothesis that ALS and FTD belong to the same disease spectrum.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Amyotrophic Lateral Sclerosis / genetics*
  • C9orf72 Protein
  • Chromosomes, Human, Pair 9*
  • DNA Repeat Expansion*
  • Female
  • Frontotemporal Dementia / genetics*
  • Genotype
  • Haplotypes
  • Humans
  • Male
  • Middle Aged
  • Mutation
  • Pedigree
  • Polymerase Chain Reaction
  • Proteins / genetics*

Substances

  • C9orf72 Protein
  • C9orf72 protein, human
  • Proteins