Association of a 12.5-kilobase allele of the MspI restriction fragment length polymorphism of the C6 gene in patients with total deficiency of the sixth component of complement.

The distribution of MspI restriction fragment length polymorphism (RFLP) alleles was investigated using the C6-PVX probe of the sixth component of complement (C6) and DNA from lymphocytes of 11 patients with homozygous C6 deficiency (C6Q0), 18 of their family members, 3 patients with subtotal C6 deficiency (C6SD) and 28 normal C6-sufficient controls. A biallelic polymorphism of 12.5- and 8.2-kb RFLP alleles was observed, and co-dominant inheritance of the two alleles was demonstrated in family studies. All 11 C6Q0 patients were homozygous for the 12.5-kb allele; this includes 8 unrelated propositi. The gene frequencies for both the 12.5- and 8.2-kb alleles in control subjects were 0.5, and the association of C6*Q0 with the 12.5-kb allele was found to be highly significant (p = 0.0001). Family studies in a C6Q0 family demonstrated that the MspI polymorphism may be used to trace C6*Q0 heterozygous carriers. Studies in families with C6SD, when considered with the results of C6 and C7 allotyping, showed definite co-segregation of C6*SD with the MspI 8.2-kb allele in one family and very probable co-segregation in another. All 11 South African C6Q0 subjects were homozygous for the C6Q0/MspI 12.5-kb/C7 M haplotype. Our data describe new associations of C6 deficiency genes which may assist in the future identification of the molecular defects.