title: Identification of CYP21A2 mutant alleles in Czech patients with 21-hydroxylase deficiency.
abstract: Congenital adrenal hyperplasia (CAH) is comprised of a group of autosomal recessive disorders caused by an enzymatic deficiency which impairs the biosynthesis of cortisol and, in most of the severe cases, also the biosynthesis of aldosterone. Approximately 90-95% of all the CAH cases are due to mutations in the steroid 21-hydroxylase gene (CYP21A2). In this study, the molecular genetic analysis of CYP21A2 was performed in 267 Czech probands suspected of 21-hydroxylase deficiency (21OHD). 21OHD was confirmed in 241 probands (2 mutations were detected). In 26 probands, a mutation was found only in 1 CYP21A2 allele. A set of 30 different mutant alleles was determined. We describe i) mutated CYP21A2 alleles carrying novel point mutations (p.Thr168Asn, p.Ser169X and p.Pro386Arg), ii) mutated CYP21A2 alleles carrying the novel chimeric gene designated as CH-7, which was detected in 21.4% of the mutant alleles, iii) an unusual genotype with a combination of the CYP21A2 duplication, 2 point mutations and the CYP21A2 large-scale gene conversion on the second allele, and (iv) a detailed analysis of the chimeric CYP21A1P/CYP21A2 genes. In conclusion, our genotyping approach allowed for the accurate identification of the CYP21A2 gene mutations in 21OHD patients and their families and provided some useful information on diagnosis and genetic counselling.
authors.affiliation: Centre of Molecular Biology and Gene Therapy, University Hospital Brno, Cernopolní 9, Brno, Czech Republic.
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Vrzalová
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Hrubá
authors.forename: Eva
authors.initials: E
authors.lastname: St'ahlová Hrabincová
authors.forename: Slavka
authors.initials: S
authors.lastname: Pouchlá
authors.forename: Felix
authors.initials: F
authors.lastname: Votava
authors.forename: Stanislava
authors.initials: S
authors.lastname: Kolousková
authors.forename: Lenka
authors.initials: L
authors.lastname: Fajkusová
mesh_terms: D000312:Adrenal Hyperplasia, Congenital / Q000175:diagnosis / Q000235:genetics*; D000483:Alleles; D018153:Czech Republic; D017353:Gene Deletion; D020440:Gene Duplication; D005838:Genotype; D006801:Humans; D009154:Mutation; D010641:Phenotype; D017354:Point Mutation; D013255:Steroid 21-Hydroxylase / Q000235:genetics*
chemical_list: C531510:CYP21A2 protein, human; D013255:Steroid 21-Hydroxylase