GENETIC BASES OF HUMAN-COMPLEMENT C7 DEFICIENCY

Complement C7 deficiency (C7D) is associated frequently with recurrent bacterial infections, especially meningitis caused by Neisseria menin gitidis. We report in this work the molecular bases of C7D in two unre lated Japanese males. We used exon-specific PCR/single-strand conforma tion polymorphism analysis as a screening step for mutations, Subseque nt direct sequencing of the target exons identified homozygous mutatio ns in exon 16 of case 1 and in exon 15 of case 2, The mutation of case 1 was a homozygous T to A transversion at nucleotide 2250, the third nucleotide of the codon TGT for Cys(728), leading to a stop codon TGA (C728X). In case 2, a homozygous 2-bp deletion (2137delTG/2138delGT/21 39deITG) caused a frameshift, generating a premature termination codon 4 to 6 nucleotides downstream, Family study in case 1 confirmed the g enetic nature of the defect, Moreover, we detected a novel polymorphis m in intron 11 that presumably is linked to the mutation responsible f or C7D in case 1, Our results indicate that the pathogenesis of C7D is heterogeneous like most of the other deficiencies of complement compo nents.