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 deficiency, a rare primary immunodeficiency, are characterized by a lack of MHC class II expression which is the result of defects in trans-acting factors. 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 of the subunits of the multimeric phosphoprotein complex, RFX. In the present study we fused fibroblasts of a recently identified MHC class II deficiency patient, OSE, with fibroblasts derived from patients representative of each of the four complementation groups. Transient heterokaryon analysis indicated that OSE belonged to complementation group C. Furthermore, transfection of wild-type RFX5 cDNA into OSE fibroblasts resulted in restoration of the defect. Mutation analysis revealed that the RFX5 mRNA lacked four nucleotides and that this deletion was the consequence of a G to A transition in a splice acceptor site. Genomic oligotyping demonstrated that OSE was homozygous for the splice site mutation.