An unequal crossover between the RCCX modules of the human MHC leading to the presence of a CYP21B gene and a tenascin TNXB/TNXA-RP2 recombinant between C4A and C4B genes in a patient with juvenile rheumatoid arthritis

The RCCX module of the human MHC class III region is comprised of four gene s arranged in tandem: RP, complement C4, steroid 21-hydroxylase (CYP21), an d tenascin X (TNX), Variations in the number and genes of the RCCX modules may lead to genetic and/or autoimmune diseases. Restriction fragment length polymorphism (RFLP) analysis was utilized to determine the RCCX modular va riation in patients with juvenile rheumatoid arthritis (JRA). In JRA patien t L1, RFLP analysis suggested the presence of a bimodular RCCX structure co ntaining both C4A long and C4B short genes, yet missing the markers for the CYP21A and TNXA genes usually located between the C4A and C4B genes. The 7 .5-kb genomic fragment spanning the CYP21-TNX-RP2 genes was cloned and sequ enced, revealing that a genetic recombination occurred between TNXA of a bi modular RCCX chromosome and TNXB of a monomodular RCCX chromosome, This rec ombination results in a new MHC haplotype with a CYP21B gene and a TNXB/TNX A-RP2 recombinant between the two C4 genes. Elucidation of the breakpoint r egion provides further evidence for the instability of the MHC class III ge ne region as a result of the RCCX modular variation.