title: DNA analysis in a MHC heterozygous patient with complete C4 deficiency--homozygosity for C4 gene deletion and C4 pseudogene.
abstract: Virtually all cases of inherited C4 deficiency appear to be caused by homozygosity for rare MHC haplotypes carrying combined defects of genes coding for the C4A and C4B isotypes. The present analysis concerned a C4-deficient patient with two different MHC haplotypes, [HLA-A2, B40, SC00, DR6] and [HLA-A30, B18, F1C00, DR3]. Digestion of genomic DNA from the patient with Taq I and probing with a 5' cDNA C4 probe and a CYP21-specific probe gave only a 7.0-kb and a 3.7-kb band, respectively. The analysis of restriction fragment length polymorphism in family members showed that both C4-deficient haplotypes contained a C4 pseudogene at the C4 locus I and a CYP21 gene together with a deletion of the C4B gene and the adjacent CYP21P gene. None of the C4 pseudogenes contained C4A- or C4B-specific nucleotide sequences as judged from hybridization studies of polymerase chain reaction products. The findings illustrate the high degree of polymorphism in C4 genes and that both gene deletions and presence of a C4 pseudogene are common as reasons for C4 null alleles. The rare C4 double null alleles appear to have arisen in different MHC haplotypes independently.
authors.affiliation: Department of Medical Microbiology, Lund University, Sweden.
authors.forename: G
authors.initials: G
authors.lastname: Nordin Fredrikson
authors.forename: L
authors.initials: L
authors.lastname: Truedsson
authors.forename: A G
authors.initials: AG
authors.lastname: Sjöholm
authors.forename: M
authors.initials: M
authors.lastname: Kjellman
mesh_terms: D000293:Adolescent; D001483:Base Sequence; D002872:Chromosome Deletion; D003181:Complement C4 / Q000172:deficiency* / Q000235:genetics*; D004247:DNA / Q000235:genetics*; D015342:DNA Probes; D005260:Female; D006680:HLA Antigens / Q000235:genetics; D006239:Haplotypes; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology; D008969:Molecular Sequence Data; D010375:Pedigree; D011544:Pseudogenes
chemical_list: D003181:Complement C4; D015342:DNA Probes; D006680:HLA Antigens; D004247:DNA