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Identification of CYP21A2 mutant alleles in Czech patients with 21-hydroxylase deficiency.
Int J Mol Med. 2010 Oct; 26(4):595-603.IJ

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+Show Affiliations

Centre of Molecular Biology and Gene Therapy, University Hospital Brno, Cernopolní 9, Brno, Czech Republic.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20818501

Citation

Vrzalová, Zuzana, et al. "Identification of CYP21A2 Mutant Alleles in Czech Patients With 21-hydroxylase Deficiency." International Journal of Molecular Medicine, vol. 26, no. 4, 2010, pp. 595-603.
Vrzalová Z, Hrubá Z, St'ahlová Hrabincová E, et al. Identification of CYP21A2 mutant alleles in Czech patients with 21-hydroxylase deficiency. Int J Mol Med. 2010;26(4):595-603.
Vrzalová, Z., Hrubá, Z., St'ahlová Hrabincová, E., Pouchlá, S., Votava, F., Kolousková, S., & Fajkusová, L. (2010). Identification of CYP21A2 mutant alleles in Czech patients with 21-hydroxylase deficiency. International Journal of Molecular Medicine, 26(4), 595-603.
Vrzalová Z, et al. Identification of CYP21A2 Mutant Alleles in Czech Patients With 21-hydroxylase Deficiency. Int J Mol Med. 2010;26(4):595-603. PubMed PMID: 20818501.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Identification of CYP21A2 mutant alleles in Czech patients with 21-hydroxylase deficiency. AU - Vrzalová,Zuzana, AU - Hrubá,Zuzana, AU - St'ahlová Hrabincová,Eva, AU - Pouchlá,Slavka, AU - Votava,Felix, AU - Kolousková,Stanislava, AU - Fajkusová,Lenka, PY - 2010/9/7/entrez PY - 2010/9/8/pubmed PY - 2011/1/11/medline SP - 595 EP - 603 JF - International journal of molecular medicine JO - Int J Mol Med VL - 26 IS - 4 N2 - 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. SN - 1791-244X UR - https://www.unboundmedicine.com/medline/citation/20818501/Identification_of_CYP21A2_mutant_alleles_in_Czech_patients_with_21_hydroxylase_deficiency_ DB - PRIME DP - Unbound Medicine ER -