A Novel Mutation in a Patient with a Deficiency of the Eighth Component of Complement Associated with Recurrent Meningococcal Meningitis
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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.
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.
This is the first report of a duplication mutation in C8β deficiency and extends the molecular heterogeneity of the disorder.
KeywordsMembrane attack complex deficiency meningitis mutation
We would like to acknowledge Steven Bishop (Immunology Laboratory, Churchill Hospital) for performing complement measurements and functional assays, the patient for allowing us to publish our findings, Dr. Ann Orren for helpful advice, and Dr A.P Gillette (Consultant Microbiologist, Stoke Mandeville Hospital) for referring the patient initially. This study was supported by monies from NIHR Biomedical Research Centre in Oxford, the Primary Immunodeficiency Association, the Jeffrey Modell Foundation and Baxterhealthcare (HC, AD, BF), and the Wellcome Trust, programme no. 068590 (BPM, AT, AR).
Conflict of interest
The authors have no conflict of interest.
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