Characterization of a large genomic deletion in four Irish families with C7 deficiency

• Published in: Molecular immunology Vol. 50; no. 1-2; pp. 57 - 59
• Main Authors: Thomas, A.D., Orren, A., Connaughton, J., Feighery, C., Morgan, B.P., Roberts, A.G.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-02-2012
• Subjects: Alleles; Base Sequence; Blotting, Western; Boundaries; Breakpoints; Complement C7 - deficiency; Complement C7 - genetics; Complement C7 - metabolism; Complement component C7; Complement deficiency; DNA Mutational Analysis; Exons; Exons - genetics; Family Health; Female; Gene deletion; genomics; Genotype; Heterozygotes; Humans; INDEL Mutation; Infection; Insertion; Insertion deletion mutations; Ireland; Male; Membrane attack complex; Mutation; Neisseria meningitidis; Pedigree; Polymerase Chain Reaction; Primers; Sequence Deletion; Ireland; Insertion deletion mutations; Membrane attack complex; Complement component C7; Complement deficiency
• ISSN: 0161-5890; 1872-9142
• DOI: 10.1016/j.molimm.2011.12.002

► The examination of four complement C7 deficient Irish families. ► The identification of the genomic basis of deficiency. ► A PCR based screening method to detect the defect in homozygotes and heterozygotes. ► This novel insertion deletion mutation may be a common cause of C7 deficiency in Ireland.
Inherited deficiency of the seventh complement component (C7) is associated with increased susceptibility to Neisseria meningitidis infections. The disease is rare in most Western countries. Here we report new investigations of a large, but incompletely characterized genomic deletion of exons 8 and 9 [c.739-?_1093+?del], previously identified in three unrelated Irish families with C7 deficiency. We have analysed DNA from one individual, who is homozygous for the deletion, by PCR using primers progressively proximal to the deleted exons. Thus we were able to map the deletion boundaries. Amplification across the breakpoint and sequencing revealed an indel mutation that included a 6.4kb deletion together with an insertion of a novel 8bp sequence [c.739+1262_1270-2387delinsGCAGGCCA]. We demonstrated the same defect in the C7 deficient patients from each family and developed a duplex PCR method to enable the detection of alleles containing the deletion in heterozygotes. A member of a fourth family was found to be homozygous for the deletion defect. Thus, the deletion defect may be a more commonly distributed cause of C7 deficiency in Ireland.