Journal Article

A Novel Mutation in a Patient with a Deficiency of the Eighth Component of Complement Associated with Recurrent Meningococcal Meningitis

Arnold, D. F., Thomas, A., Ferry, B., Chapel, H., Morgan, B. P., Roberts, A. G.

2009

Overview

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 α–γ deficiency has been predominantly reported amongst Afro-Caribbeans, Hispanics, and Japanese and C8β 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 C8β. In genetic studies, the common exon 9 C > T transition responsible for 85% of C8β 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 C8β deficiency and extends the molecular heterogeneity of the disorder.

• Publisher: Springer US,Springer Nature B.V
• Subject: Adolescent / Antibiotic Prophylaxis / Biomedical and Life Sciences / Biomedicine / Codon, Nonsense / Complement C8 - genetics / Complement C8 - immunology / Complement C8 - metabolism / Cytotoxicity, Immunologic - genetics / DNA Mutational Analysis / Genetic Predisposition to Disease / Haemophilus Vaccines - administration & dosage / Humans / Immunologic Deficiency Syndromes - complications / Immunologic Deficiency Syndromes - genetics / Immunologic Deficiency Syndromes - immunology / Immunologic Deficiency Syndromes - physiopathology / Immunologic Deficiency Syndromes - therapy / Immunology / Immunotherapy / Infectious Diseases / Internal Medicine / Male / Medical Microbiology / Meningitis, Meningococcal - complications / Meningitis, Meningococcal - genetics / Meningitis, Meningococcal - immunology / Meningitis, Meningococcal - physiopathology / Meningitis, Meningococcal - therapy / Neisseria / Neisseria meningitidis / Penicillins - therapeutic use / Pneumococcal Vaccines - administration & dosage / Recurrence / Sepsis