Detection of heterozygous C8 beta deficiency by PCR in a healthy Italian population

In Italy a rather high number of homozygotes with late complement component defects has been found among patients with meningococcal disease. It seems that clinical manifestations of meningococcal disease are less severe in patients with complement deficiency than in normal individuals. This situation could even be more evident in the heterozygous carriers for whom a selective advantage is discussed. In this study we have screened a cohort of 527 Italian blood donors from western Sicily for the presence of C8B mutated allele. Heterozygotes for C8 beta deficiency were identified using a specific PCR assay to detect a C-->T transition in exon 9 of the C8B gene. This mutation represents the most frequent genetic mechanism for C8 beta deficiency in Caucasians. A rapid PCR screening test was performed on DNA extracted from pooled blood samples of up to 8 individuals. A single male individual with heterozygous C8 beta deficiency was detected. In the family studies it was shown that his two brothers and the mother were heterozygous carriers too. Functional activity of the classical and alternative complement pathways were normal. No neisserial infections or inflammatory diseases were found in the family history. It was shown that the allele-specific PCR is a sensitive and rapid method to examine large numbers of DNA samples. It permitted to assess the real prevalence of the C8B mutated null allele in the general population free of ascertainment bias.