A family with complement factor D deficiency

A complement factor D deficiency was found in a young woman who had experie nced a serious Neisseria meningitidis infection, in a deceased family membe r with a history of meningitis, and in three relatives without a history of serious infections. The patient and these three relatives showed a normal activity of the classical complement pathway, but a very low activity of th e alternative complement pathway and a very low capacity to opsonize Escher ichia coli and N. meningitidis (isolated from the patient) for phagocytosis by normal human neutrophils. The alternative pathway-dependent hemolytic a ctivity and the opsonizing capacity of these sera were restored by addition of purified factor D. The family had a high degree of consanguinity, and s everal other family members exhibited decreased levels of factor D. The gen e encoding factor D was found to contain a point mutation that changed the TCG codon for serine 42 into a TAG stop codon, This mutation was found in b oth alleles of the five completely factor D-deficient family members and in one allele of 21 other members of the same family who had decreased or low -normal factor D levels in their serum. The gene sequence of the signal pep tide of human factor D was also identified. Our report is the first, to our knowledge, to document a Factor D gene mutation. The mode of inheritance o f factor D deficiency is autosomal recessive, in accordance with the locali zation of the Factor D gene on chromosome 19. Increased susceptibility for infections in individuals with a partial factor D deficiency is unlikely.