title: Complement factor 5 (C5) p.A252T mutation is prevalent in, but not restricted to, sub-Saharan Africa: implications for the susceptibility to meningococcal disease.
abstract: 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.
authors.affiliation: Immunology Division, Department of Cell Biology, Physiology and Immunology, Hospital Universitari Vall d'Hebron (HUVH), Vall d'Hebron Research Institute (VHIR), Autonomous University of Barcelona (UAB), Barcelona, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Franco-Jarava
authors.affiliation: Departament de Ciències Experimentals i de la Salut, Institut de Biologia Evolutiva (CSIC-UPF), Universitat Pompeu Fabra, Barcelona, Spain.
authors.forename: D
authors.initials: D
authors.lastname: Comas
authors.affiliation: Department of Clinical Sciences, University of Cape Town, Cape Town, South Africa.|Institute of Infection and Immunity, Cardiff University, Cardiff, UK.|Allergy Diagnostic and Clinical Research Unit, Department of Medicine, Lung Institute, University of Cape Town, Cape Town, South Africa.
authors.forename: A
authors.initials: A
authors.lastname: Orren
authors.affiliation: Immunology Division, Department of Cell Biology, Physiology and Immunology, Hospital Universitari Vall d'Hebron (HUVH), Vall d'Hebron Research Institute (VHIR), Autonomous University of Barcelona (UAB), Barcelona, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Hernández-González
authors.affiliation: Immunology Division, Department of Cell Biology, Physiology and Immunology, Hospital Universitari Vall d'Hebron (HUVH), Vall d'Hebron Research Institute (VHIR), Autonomous University of Barcelona (UAB), Barcelona, Spain.
authors.forename: R
authors.identifier: 0000-0002-5964-536X
authors.initials: R
authors.lastname: Colobran
mesh_terms: D044383:Black People / Q000235:genetics*; D003182:Complement C5 / Q000172:deficiency* / Q000235:genetics*; D004198:Disease Susceptibility; D005787:Gene Frequency; D000081208:Hereditary Complement Deficiency Diseases; D006579:Heterozygote; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000453:epidemiology* / Q000235:genetics*; D008403:Mass Screening; D008585:Meningitis, Meningococcal / Q000235:genetics*; D009154:Mutation; D013019:South Africa
chemical_list: D003182:Complement C5
keywords: Africa; C5 deficiency; complement; infection; meningococcal disease; primary immunodeficiency