NONSENSE MUTATION IN EXON-4 OF HUMAN-COMPLEMENT C9 GENE IS THE MAJOR CAUSE OF JAPANESE COMPLEMENT C9 DEFICIENCY

Deficiency of the ninth component of human complement (C9) is the most common complement deficiency in Japan but is rare in other countries. We studied the molecular basis of C9 deficiency in four Japanese C9-d eficient patients who had suffered from meningococcal meningitis. Dire ct sequencing of amplified C9 cDNA and DNA revealed a nonsense substit ution (CGA --> TGA) at codon 95 in exon 4 in the four CB-deficient ind ividuals. An allele-specific polymerase chain reaction system designed to detect exclusively only one of the normal and mutant alleles indic ated that all the four patients were homozygous for the mutation in ex on 4 and that the parents of patient 2 were heterozygous. The common m utation at codon 95 in exon 4 might be responsible for most Japanese C 9 deficiency.