Molecular characterisation of C4 null alleles found in Felty's syndrome

A higher prevalence of C4B null alleles is found in Felty's syndrome. The molecular basis of C4 null alleles was investigated by studying restriction fragment length polymorphisms (RFLPs) obtained with C4 and 21-hydroxylase (21-OH) DNA probes and by pulsed field gel electrophoresis in 30 subjects with Felty's syndrome. C4A null alleles were found in 10 subjects, and in five of these were associated with a deletion that included C4A and adjacent 21-OHA gene sequences. A 6.4 kilobase C4B-5'-specific Taq I fragment usually provided a reliable guide to the presence of a C4A deletion but unusually in one instance this fragment was found to be a marker of a functioning C4A gene. A C4B null allele was found in 17 subjects and was associated with a deletion involving C4B and 21-OHA gene sequences on only two occasions. There were no instances in which deletion of the 21-OHB gene occurred.