Mutation in a winged-helix DNA-binding motif causes atypical bare lymphocyte syndrome.
Bare lymphocyte syndrome (BLS) is an autosomal recessive severe-combined immunodeficiency that can result from mutations in four different transcription factors that regulate the expression of major histocompatibility complex (MHC) class II genes. We have identified here the defective gene that is responsible for the phenotype of the putative fifth BLS complementation group. The mutation was found in the regulatory factor that binds X-box 5 (RFX5) and was mapped to one of the arginines in a DNA-binding surface of this protein. Its wild-type counterpart restored binding of the RFX complex to DNA, transcription of all MHC class II genes and the appearance of these determinants on the surface of BLS cells.
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001120:Arginine / Q000737:chemistry; D001665:Binding Sites; D002051:Burkitt Lymphoma / Q000473:pathology; D002461:Cell Line, Transformed; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D005802:Genes, MHC Class II; D005816:Genetic Complementation Test; D006681:HLA-D Antigens / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D011487:Protein Conformation; D000071701:Regulatory Factor X Transcription Factors; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D016511:Severe Combined Immunodeficiency / Q000145:classification / Q000235:genetics*; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D006681:HLA-D Antigens; C093524:RFX5 protein, human; D000071701:Regulatory Factor X Transcription Factors; D004247:DNA; D001120:Arginine