title: Major-histocompatibility-complex gene markers and restriction-fragment analysis of steroid 21-hydroxylase (CYP21) and complement C4 genes in classical congenital adrenal hyperplasia patients in a single population.
abstract: The gene CYP21B, encoding the steroid 21-hydroxylase enzyme of adrenal steroid biosynthesis, has been mapped to the human major histocompatibility complex (MHC). Deficiency of this enzyme leads to congenital adrenal hyperplasia (CAH). We report the phenotypes of the HLA and complement C4 and Bf genes, which are closely linked to the CYP21B gene, together with a detailed analysis of the CYP21 and C4 RFLP, in 17 Finnish families with CAH. The RFLP analysis with six restriction enzymes suggested that, altogether, 35% of the affected chromosomes had a CYP21B + C4B gene deletion, 9% an obvious gene conversion of the CYP21B gene to a CYP21A-like gene, and 3% a CYP21A + C4B duplication. The remaining 53% gave the RFLP patterns also found in nonaffected chromosomes. We also found that a 14.0-kb EcoRI RFLP marker of the CYP21 genes was strongly associated with the presence of a short C4B gene, suggesting that some of the RFLP markers found with the CYP21 probe may actually derive from C4B gene polymorphism. Three particular MHC haplotypes, each with a characteristic RFLP pattern, were found in many unrelated families. These three haplotypes accounted for 59% of the affected chromosomes in our study group, the rest (41%) of the affected chromosomes being distributed among various subtypes. The results suggest that, within a single, well-defined population such as in Finland, only a few CYP21B gene defects may constitute a substantial part of the affected chromosomes. This finding will help in genetic studies of CAH in such populations.
authors.affiliation: Finnish Red Cross Blood Transfusion Service, Tissue Typing Laboratory, Helsinki, Finland.
authors.forename: J
authors.initials: J
authors.lastname: Partanen
authors.forename: S
authors.initials: S
authors.lastname: Koskimies
authors.forename: I
authors.initials: I
authors.lastname: Sipilä
authors.forename: V
authors.initials: V
authors.lastname: Lipsanen
mesh_terms: D000312:Adrenal Hyperplasia, Congenital / Q000235:genetics*; D002872:Chromosome Deletion; D003181:Complement C4 / Q000235:genetics*; D005787:Gene Frequency; D006580:Genetic Carrier Screening; D008040:Genetic Linkage; D005819:Genetic Markers; D006680:HLA Antigens / Q000235:genetics*; D006801:Humans; D010641:Phenotype; D012150:Polymorphism, Restriction Fragment Length; D013255:Steroid 21-Hydroxylase / Q000235:genetics*; D013250:Steroid Hydroxylases / Q000235:genetics*
chemical_list: D003181:Complement C4; D005819:Genetic Markers; D006680:HLA Antigens; D013250:Steroid Hydroxylases; D013255:Steroid 21-Hydroxylase