title: Restricted genetic defects underlie human complement C6 deficiency.
abstract: 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.
authors.affiliation: Département d'Immunologie, Hôpital Européen Georges Pompidou, INSERM U430, France.
authors.forename: M A
authors.initials: MA
authors.lastname: Dragon-Durey
authors.forename: V
authors.initials: V
authors.lastname: Fremeaux-Bacchi
authors.forename: J
authors.initials: J
authors.lastname: Blouin
authors.forename: D
authors.initials: D
authors.lastname: Barraud
authors.forename: W H
authors.initials: WH
authors.lastname: Fridman
authors.forename: M D
authors.initials: MD
authors.lastname: Kazatchkine
mesh_terms: D000293:Adolescent; D000328:Adult; D000349:Africa / Q000208:ethnology; D002648:Child; D002675:Child, Preschool; D003183:Complement C6 / Q000172:deficiency* / Q000235:genetics*; D005091:Exons; D005602:France; D017353:Gene Deletion; D005923:Glomerulosclerosis, Focal Segmental / Q000276:immunology; D006720:Homozygote; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000276:immunology; D008585:Meningitis, Meningococcal / Q000276:immunology; D017422:Sequence Analysis, DNA; D016706:Still's Disease, Adult-Onset / Q000276:immunology
chemical_list: D003183:Complement C6