Restricted genetic defects underlie human complement C6 deficiency

Abstract

SUMMARY Complement C6 homozygous deficiency (C6D) has been rarely observed in Caucasians but was reported at higher prevalence among African‐Americans. We report on the molecular basis of C6D in seven unrelated black individuals of North or Central Africa descent who live in France. These patients have presented Neisseria meningitidis infection (four cases), focal and segmental glomerulosclerosis with hyalinosis (one case), systemic lupus erythematosus (one case) or Still's disease (one case). All patients exhibited undetectable antigenic C6 by using a sensitive ELISA assay. An additional four cases of complete C6 deficiency with no associated disease have been characterized after family studies. Exons 6, 7 and 12 have been described recently as the location of molecular defects on the C6 gene in randomly chosen black Americans. Genomic DNA from the seven patients were subjected to direct polymerase chain reaction amplification of these three exons. Nucleotide sequencing analysis of the amplified DNA fragments revealed a homozygous single‐base deletion (1936delG) in exon 12 in three cases and four compound heterozygous deletions for a single base in exon 7 (1195delC) or in exon 6 (878delA) associated with the same deletion in exon 12 (1936delG). Our observations further establish the restricted pattern of genetic defects associated with homozygous C6 complement deficiency in individuals of African descent.

Hereditary complement C7 deficiency in nine families: Subtotal C7 deficiency revisited

“…While defects in the C2 and C6 genes are known to be associated to a few mutation hot spots [19,20], C7 mutations seem more heterogeneous. In agreement with the relative diversity of molecular defects observed previously carried by the C7 gene, we found three novel mutations expected to be deleterious for C7 protein production or function.…”

TRAF1/C5polymorphism is not associated with pemphigus

“…C5 sera concentration was measured by a rabbit double‐ligand enzyme‐linked immunosorbent assay (ELISA) test (home‐made) using a polyclonal anti‐human C5 antibody (Calbiochem, Meudon, France) 6 . Results were expressed as percentages according to a pool of 100 healthy controls.…”

Nucleotide Sequence Analyses of Human Complement 6 (C6) Gene Suggest Balancing Selection

“…Complement activation plays an important role in the pathogenesis of several pathological processes, such as ischemia and reperfusion injury occurring in myocardial infarction and stroke, hyperacute graft rejection and antibody‐mediated autoimmune diseases (Nauta et al 2002). On the other hand, deficiencies of C6 result in remarkable susceptibility to meningococcal infections or development of autoimmune diseases (Dragon‐Durey et al 2003) (C6 deficiency [MIM 217050]). In addition to a cytolytic function, recent studies suggested a role of the MAC in the cell cycle and apoptosis (Rus et al 2001).…”