C9orf72 repeat expansions in South Africans with amyotrophic lateral sclerosis

• Published in: Journal of the neurological sciences Vol. 401; pp. 51 - 54
• Main Authors: Nel, Melissa, Agenbag, Gloudi M., Henning, Franclo, Cross, Helen M., Esterhuizen, Alina, Heckmann, Jeannine M.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.06.2019
• Subjects: Africa; Aged; Amyotrophic Lateral Sclerosis - diagnosis; Amyotrophic Lateral Sclerosis - epidemiology; Amyotrophic Lateral Sclerosis - genetics; Asian People - genetics; Black or African American; Black People - genetics; C9orf72; C9orf72 Protein - genetics; Cohort Studies; DNA Repeat Expansion - genetics; Female; Gene; Humans; Male; Middle Aged; Motor neuron disease; Mutation; Neurology; South Africa - epidemiology; White People - genetics; South Africa; PMA; Africa; Motor neuron disease; ALS; SA; Gene; ANOVA; PLS; FTD; RP-PCR; Mutation; FA; HD; M/A; US; C9orf72; United States; Progressive muscular atrophy; Fronto-temporal dementia; Mixed-African; Primary lateral sclerosis; South Africa(n); Amyotrophic lateral sclerosis; Repeat primed polymerase chain reaction; Huntington's disease; Flail arm; Analysis of variance
• ISSN: 0022-510X; 1878-5883; 1878-5883
• DOI: 10.1016/j.jns.2019.04.026

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. •143 South Africans with ALS underwent C9orf72 repeat expansion genotyping.•Familial ALS was uncommon (2%) and these cases had normal C9orf72 alleles.•C9-expansions (>30 repeats) were found in 7% of cases with sporadic ALS.•C9-expansions were not found in 24 black Africans with ALS.