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INTRODUCTION: Complement component C8 is one of the five terminal complement components required for the formation of the membrane attack complex. Complete absence of C8 results in increased susceptibility to gram-negative bacteria such as Neisseria species. MATERIALS AND METHODS: Two functionally distinct C8 deficiency states have been described: C8 alpha-gamma deficiency has been predominantly reported amongst Afro-Caribbeans, Hispanics, and Japanese and C8beta mainly in Caucasians. RESULTS: We report a case of functional and immunochemical deficiency of the complement component C8, diagnosed in a Caucasian adult following three episodes of meningitis. Western blotting and hemolytic assay demonstrated absence of C8beta. In genetic studies, the common exon 9 C > T transition responsible for 85% of C8beta deficiencies was not found. Two mutations were identified: a novel duplication mutation, c.1047_1053 dupGGCTGTG in exon 7 that introduces a frame shift, resulting in the addition of seven novel amino acid residues and a premature stop codon, and a previously reported mutation, c.271C > T in exon 3. The parents each expressed one of these mutations, confirming compound heterozygosity. DISCUSSION: This is the first report of a duplication mutation in C8beta deficiency and extends the molecular heterogeneity of the disorder.

Original publication

DOI

10.1007/s10875-009-9295-7

Type

Journal article

Journal

J Clin Immunol

Publication Date

09/2009

Volume

29

Pages

691 - 695

Keywords

Adolescent, Antibiotic Prophylaxis, Codon, Nonsense, Complement C8, Cytotoxicity, Immunologic, DNA Mutational Analysis, Genetic Predisposition to Disease, Haemophilus Vaccines, Humans, Immunologic Deficiency Syndromes, Immunotherapy, Male, Meningitis, Meningococcal, Penicillins, Pneumococcal Vaccines, Recurrence, Sepsis