Complement factor 5 (C5) p.A252T mutation is prevalent in, but not restricted to, sub‐Saharan Africa: implications for the susceptibility to meningococcal disease

• Published in: Clinical and experimental immunology 2017-08, Vol.189 (2), p.226-231
• Main Authors: Franco‐Jarava, C., Comas, D., Orren, A., Hernández‐González, M., Colobran, R.
• Format: Article
• Language: English
• Subjects: Africa; African Continental Ancestry Group - genetics; C5 deficiency; complement; Complement C5 - deficiency; Complement C5 - genetics; Complement component 5; Complement component C5; Disease Susceptibility; Gene Frequency; Heterozygosity; Heterozygote; Humans; Immunodeficiency; Immunologic Deficiency Syndromes - epidemiology; Immunologic Deficiency Syndromes - genetics; infection; Malalties immunològiques; Mass Screening; Meningitis; Meningitis, Meningococcal - genetics; Meningococcal disease; Mutation; Original; Polymerase chain reaction; Population genetics; Primary immunodeficiencies; primary immunodeficiency; Prophylaxis; South Africa; Vaccines; Àfrica
• ISSN: 0009-9104; 1365-2249
• DOI: 10.1111/cei.12967

Summary Complement C5 deficiency (C5D) is a rare primary immunodeficiency associated with recurrent infections, particularly meningitis, by Neisseria species. To date, studies to elucidate the molecular basis of hereditary C5D have included fewer than 40 families, and most C5 mutations (13 of 17) have been found in single families. However, the recently described C5 p.A252T mutation is reported to be associated with approximately 7% of meningococcal disease cases in South Africa. This finding raises the question of whether the mutation may be prevalent in other parts of Africa or other continental regions. The aim of this study was to investigate the prevalence of C5 p.A252T in Africa and other regions and discuss the implications for prophylaxis against meningococcal disease. In total, 2710 samples from healthy donors within various populations worldwide were analysed by quantitative polymerase chain reaction (qPCR) assay to detect the C5 p.A252T mutation. Eleven samples were found to be heterozygous for p.A252T, and nine of these samples were from sub‐Saharan African populations (allele frequency 0·94%). Interestingly, two other heterozygous samples were from individuals in populations outside Africa (Israel and Pakistan). These findings, together with data from genomic variation databases, indicate a 0·5–2% prevalence of the C5 p.A252T mutation in heterozygosity in sub‐Saharan Africa. Therefore, this mutation may have a relevant role in meningococcal disease susceptibility in this geographical area. We analysed the complement factor 5 (C5) p.A252T mutation in 2710 samples from healthy donors worldwide and we found eleven heterozygous samples for the C5 p.A252T mutation. Nine carriers of C5 p.A252T mutation were from Sub‐Saharan African populations, indicating that heterozygosity for C5 p.A252T mutation in Sub‐Saharan Africa range from 0.5 to 2%. This mutation plays a relevant role in meningococcal disease susceptibility.