title: Prevalence of mutations leading to complete C6 deficiency (C6Q0) in the Western Cape, South Africa and detection of novel mutations leading to C6Q0 in an Irish family.
abstract: Complement component C6 is one of five terminal complement components incorporated into the membrane attack complex. Complete deficiency of C6 (C6Q0) leads to an increased susceptibility to Neisseria meningitidis infections, and affected individuals typically present with recurrent meningococcal disease. There is a relatively high prevalence of C6Q0 in the Western Cape, South Africa and three frameshift mutations have previously been described to be responsible for C6Q0 in this area-879delG, 1195delC, and 1936delG (current nomenclature). We have now genotyped a further nine genetically independent individuals with C6Q0, confirming previous reports that the most common defect in the Western Cape is 879delG. Moreover, we report the first identification of the 878delA mutation within the Western Cape, which has previously only been reported in individuals of African descent living in the United States or Europe. We also investigated the genotype of an Irish C6Q0 individual and her sibling, and report two previously undescribed mutations. One mutation alters a tyrosine codon to a stop codon within exon 10. The second mutation is within the 5' donor splice site of intron 3, and would, in all probability, disrupt splicing. These two mutations were shown to segregate independently. We also discuss the nomenclature for reporting C6 and C7 gene mutations, as the current nomenclature does not follow the recognised guidelines.
authors.affiliation: Department of Medical Biochemistry, Cardiff University and University Hospital of Wales, Heath Park, Cardiff CF14 4XW, United Kingdom. Kelly.Parham@CardiffandVale.wales.nhs.uk
authors.forename: Kelly L
authors.initials: KL
authors.lastname: Parham
authors.forename: Andrew
authors.initials: A
authors.lastname: Roberts
authors.forename: Andrew
authors.initials: A
authors.lastname: Thomas
authors.forename: Reinhard
authors.initials: R
authors.lastname: Würzner
authors.forename: Howard E
authors.initials: HE
authors.lastname: Henderson
authors.forename: Paul C
authors.initials: PC
authors.lastname: Potter
authors.forename: B Paul
authors.initials: BP
authors.lastname: Morgan
authors.forename: Ann
authors.initials: A
authors.lastname: Orren
mesh_terms: D003183:Complement C6 / Q000737:chemistry / Q000172:deficiency / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D008589:Meningococcal Infections / Q000235:genetics*; D009154:Mutation; D009345:Neisseria meningitidis; D010375:Pedigree; D013019:South Africa; D014443:Tyrosine / Q000737:chemistry / Q000235:genetics
chemical_list: D003183:Complement C6; D014443:Tyrosine