C5 complement deficiency in a Spanish family. Molecular characterization of the double mutation responsible for the defect

Abstract

The complement C5 deficiency is a recessive autosomal defect associated with recurrent infectious episodes, generally caused by Gram-negative micro-organisms. To date, only two mutations responsible for C5 deficiency have been characterized, both in heterozygosis. In this paper, we evaluate by immunochemical methods the C5 deficiency in a six-member family, in which one member suffered from meningococcal sepsis and several pneumonia episodes; and a second one with two bacterial meningitis episodes and frequent tonsillitis, pneumonia and herpetic episodes. We also characterize the molecular basis of this deficiency. No C5 protein was found in the serum from three of the children. They were found to be homozygous for a double mutation in the exon 40 of the C5 gene. The parents and the other children have half-normal levels of C5, and they were heterozygotes for the double mutation. This mutation modifies the reading frame, leading to a premature stop codon, and the resulting protein lacks 50 amino acids. As a result, homozygotes and heterozygotes have a total or a partial C5 deficiency respectively. This is the first report of a whole molecular characterization of C5 deficiency.