A Unique Recombination Event Resulting in a C 4 A * QO , C 4 B * QO Double Null Haplotype

The fourth component of complement (C4) is encoded by two closely linked genes (C4A and C4B) within the MHC. Null alleles at either locus (C4AQOor C4BQO)are relatively common, occurring at the C4A locus in 10% of normal individuals and at the C4B locus in 16% of normal individuals. However, the presence of the double null haplotype (C4A * QO,B* QO) on the same chromosome is extremely rare. Werecently studied a 7-yr-old patient with recurrent sinopulmonary infections in whomwe documented the mechanism by which the C4A* QO,B* QOdouble null haplotype arose. Evaluation revealed significantly reduced levels of both C4 antigen and C4 hemolytic activity. Analysis of extended haplotypes in the family was performed using MHCtyping and genomic DNA analysis. The patient was found to have a C4A* 3,B* QOhaplotype and a C4A* QOB*QOhaplotype. The C4A* 3,B* QO haplotype was contributed by the father. The mother possessed a C4A* QO,B* I haplotype and a C4A* 3,B* I haplotype. The first maternal haplotype was involved in a recombination event within the C4B locus on her other chromosome and resulted in a new C4B*QO null allele and the patient's C4A* QO,B* QO haplotype. Segregation analysis mapped the recombination to a region 3' to the unique 6.4-kb TaqI restriction fragment of the maternal C4B locus. This is the first demonstration of a recombination event producing a C4 double null haplotype. (J. Clin. Invest. 1992. 90:1180-1184.)