Molecular analysis of an MHC class II deficiency patient reveals a novel mutation in the RFX5 gene

Patients suffering from major histocompatibility complex (MHC) class II def iciency, a rare primary immunodeficiency, are characterized by a lack of MH C class II expression which is the result of defects in trans-acting factor s. At least four complementation groups, A, B, C, and D, can be discerned. The gene affected in group C patients is known to be RFX5 and encodes one o f the subunits of the multimeric phosphoprotein complex, RFX; In the presen t study we fused fibroblasts of a recently identified MHC class II deficien cy patient, OSE, with fibroblasts derived from patients representative of e ach of the four complementation groups. Transient heterokaryon analysis ind icated that OSE belonged to complementation group C. Furthermore, transfect ion of wild-type RFX5 cDNA into OSE fibroblasts resulted in restoration of the defect. Mutation analysis revealed that the RFX5 mRNA lacked four nucle otides and that this deletion was the consequence of a G to A transition in a splice acceptor site. Genomic oligotyping demonstrated that OSE was homo zygous for the splice site mutation.