title: A family with complement factor D deficiency.
abstract: A complement factor D deficiency was found in a young woman who had experienced a serious Neisseria meningitidis infection, in a deceased family member 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 the alternative complement pathway and a very low capacity to opsonize Escherichia coli and N. meningitidis (isolated from the patient) for phagocytosis by normal human neutrophils. The alternative pathway-dependent hemolytic activity and the opsonizing capacity of these sera were restored by addition of purified factor D. The family had a high degree of consanguinity, and several other family members exhibited decreased levels of factor D. The gene 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 both 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 peptide 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 of factor D deficiency is autosomal recessive, in accordance with the localization of the Factor D gene on chromosome 19. Increased susceptibility for infections in individuals with a partial factor D deficiency is unlikely.
authors.affiliation: Department of Internal Medicine, St. Antonius Hospital, Nieuwegein, The Netherlands. d.biesma@antonius.net
authors.forename: D H
authors.initials: DH
authors.lastname: Biesma
authors.forename: A J
authors.initials: AJ
authors.lastname: Hannema
authors.forename: H
authors.initials: H
authors.lastname: van Velzen-Blad
authors.forename: L
authors.initials: L
authors.lastname: Mulder
authors.forename: R
authors.initials: R
authors.lastname: van Zwieten
authors.forename: I
authors.initials: I
authors.lastname: Kluijt
authors.forename: D
authors.initials: D
authors.lastname: Roos
mesh_terms: D000328:Adult; D001483:Base Sequence; D011416:Complement Factor D / Q000737:chemistry / Q000172:deficiency* / Q000235:genetics; D015941:Complement Hemolytic Activity Assay; D003241:Consanguinity; D018076:DNA, Complementary / Q000737:chemistry; D004438:Ecchymosis / Q000473:pathology; D005260:Female; D006801:Humans; D007154:Immune System Diseases / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D008969:Molecular Sequence Data; D010375:Pedigree; D017354:Point Mutation
chemical_list: D018076:DNA, Complementary; C493488:CFD protein, human; D011416:Complement Factor D