C9orf72 repeat expansions in South Africans with amyotrophic lateral sclerosis

J Neurol Sci. 2019 Jun 15:401:51-54. doi: 10.1016/j.jns.2019.04.026. Epub 2019 Apr 17.

Abstract

The hexanucleotide repeat expansion in the C9orf72 gene is the most common genetic variant found in individuals with sporadic amyotrophic lateral sclerosis (ALS), occurring at a frequency of between 7 and 11% in cohorts of European ancestry. While limited data suggest that C9-expansions (>30 repeats) are less frequent in African-Americans with ALS, there is no data on the frequency of C9-expansions among ALS subjects residing in Africa. We therefore investigated the frequency of this expansion mutation (using repeat-primed PCR) in a cohort of 143 South Africans (SA) with ALS. The cohort included different genetic ancestry subgroups who self-identified as black African (n = 24), Cape mixed-African (M/A) (n = 65), white European ancestry (n = 51), and Indian ancestry (n = 3). Three M/A individuals had a family history of ALS (2%) and all had normal C9orf72 alleles. Of the 140 individuals with sporadic ALS who were successfully genotyped, 10 (7%) carried pathogenic C9-expansions; four white and six M/A ancestry individuals, respectively. Our results highlight the importance of including Africans in genetic studies aimed at unravelling the genomic architecture in ALS and suggest pathogenetic mechanisms other than the C9orf72 expansion in black Africans with ALS.

Keywords: Africa; C9orf72; Gene; Motor neuron disease; Mutation.

MeSH terms

  • Aged
  • Amyotrophic Lateral Sclerosis / diagnosis
  • Amyotrophic Lateral Sclerosis / epidemiology*
  • Amyotrophic Lateral Sclerosis / genetics*
  • Asian People / genetics
  • Black People / genetics*
  • Black or African American
  • C9orf72 Protein / genetics*
  • Cohort Studies
  • DNA Repeat Expansion / genetics*
  • Female
  • Humans
  • Male
  • Middle Aged
  • South Africa / epidemiology
  • White People / genetics

Substances

  • C9orf72 Protein
  • C9orf72 protein, human