DIFFICULTIES IN THE ASCERTAINMENT OF C9 DEFICIENCY - LESSONS TO BE DRAWN FROM A COMPOUND HETEROZYGOTE C9-DEFICIENT SUBJECT

A group of patients with long-surviving mismatched kidney allografts w ere investigated for complement function using haemolytic assays in ag arose gels. One patient was found to have no alternative pathway activ ity but a low normal classical pathway. Surprisingly, investigation re vealed that the patient's complement was normal for all components exc ept C9, which was functionally absent. The patient was shown to be het erozygous for DNA markers in the C6, C7 and C9 region of chromosome 5 and therefore appears to be a compound heterozygote for two uncharacte rized C9 deficiency genes. Serological analysis by ELISA revealed that he has trace concentrations of a non-functional C9 molecule. Western blot analysis was not sufficiently sensitive to permit detection of th is molecule. We hypothesize that the patient is heterozygous for a com plete deficiency of C9 and for a gene directing hyposynthesis of a def ective C9. We also suggest that C9 deficiency may be more common among Caucasians than has been reported.