title: Molecular analysis of patient and carrier genes with congenital steroid 21-hydroxylase deficiency by using polymerase chain reaction and single strand conformation polymorphism.
abstract: Steroid 21-hydroxylase deficiency is a major cause of congenital adrenal hyperplasia and is caused by genetic impairment of this enzyme. Since approximately 80% of cases are caused by point mutations of the CYP21B (CYP21A2) gene, whereas the remaining 20% are due to deletion of this gene, we used the polymerase chain reaction single strand conformation polymorphism technique for rapid and accurate diagnosis of this disease. Of 23 patients examined, 1 had a hemizygous CYP21B gene. 18 patient's genes localized their harmful mutations or deletion on both the alleles, while 4 of them found their causative mutations on one of the two alleles, and 1 failed to find any responsible mutation. All the mutations (four nucleotide substitutions) detected are also found in the CYP21A (CYP21A1) pseudogene. A mutation at the intron 2 site is most prevalent in both salt-wasting and simple virilizing forms of the disease, and accounts for 37% of the patient's genes (17/46). Pedigree analysis of these mutations revealed that the mutations (at least four of them) occurred de novo at a considerable frequency on both the paternally and maternally inherited chromosomes. This result could explain occasional discordance of the diagnosis using HLA typing with the clinical symptoms.
authors.affiliation: Department of Chemistry, Faculty of Science, Tohoku University, Sendai, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Tajima
authors.forename: K
authors.initials: K
authors.lastname: Fujieda
authors.forename: K
authors.initials: K
authors.lastname: Nakayama
authors.forename: Y
authors.initials: Y
authors.lastname: Fujii-Kuriyama
mesh_terms: D000312:Adrenal Hyperplasia, Congenital / Q000175:diagnosis* / Q000201:enzymology / Q000235:genetics*; D000483:Alleles; D001483:Base Sequence; D017931:DNA Primers; D005091:Exons / Q000235:genetics; D005260:Female; D006579:Heterozygote; D006801:Humans; D007438:Introns / Q000235:genetics; D008297:Male; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009690:Nucleic Acid Conformation; D010375:Pedigree; D017354:Point Mutation; D016133:Polymerase Chain Reaction / Q000379:methods; D011544:Pseudogenes; D017422:Sequence Analysis, DNA; D013255:Steroid 21-Hydroxylase / Q000235:genetics*
chemical_list: D017931:DNA Primers; D013255:Steroid 21-Hydroxylase