Mutations in Steroid 21-Hydroxylase (CYP21)
- 1 January 1994
- journal article
- review article
- Published by Hindawi Limited in Human Mutation
- Vol. 3 (4) , 373-378
- https://doi.org/10.1002/humu.1380030408
Abstract
The inherited inability to synthesize cortisol is termed congenital adrenal hyperplasia. More than 90% of cases are caused by 21‐hydroxylase deficiency. This syndrome is characterized by signs of androgen excess and often mineralocorticoid deficiency. Steroid 21‐hydroxylase (P450c2l) is a microsomal enzyme expressed in the adrenal gland that catalyzes conversion of 17‐hydroxyprogesterone and progesterone to 11‐deoxycortisol and deoxycorticosterone respectively. In man, this enzyme is encoded by the CYP21 (CYP21B) gene which is located in the HLA major histocompatibility complex along with a pseudogene, CYP21P (CYP21A). Mutations in CYP21 causing congenital adrenal hyperplasia are almost all generated by recombinations between CYP21 and CYP21P. These recombinations either delete CYP21 or transfer deleterious mutations from CYP21P to CYP21, a process termed apparent gene conversion. The degree of enzymatic compromise caused by each mutation is correlated with the clinical severity of the deficiency observed in patients carrying that mutation.Keywords
This publication has 28 references indexed in Scilit:
- Molecular analysis of patient and carrier genes with congenital steroid 21-hydroxylase deficiency by using polymerase chain reaction and single strand conformation polymorphism.Journal of Clinical Investigation, 1993
- Crystal Structure of Hemoprotein Domain of P450BM-3, a Prototype for Microsomal P450'sScience, 1993
- Tenascin-X: a novel extracellular matrix protein encoded by the human XB gene overlapping P450c21BThe Journal of cell biology, 1993
- A de novo pathological point mutation at the 21–hydroxylase locus: implications for gene conversion in the human genomeNature Genetics, 1993
- Disease expression and molecular genotype in congenital adrenal hyperplasia due to 21-hydroxylase deficiency.Journal of Clinical Investigation, 1992
- Mutations of P450c21 (steroid 21-hydroxylase) at Cys428, Val281, and Ser268 result in complete, partial, or no loss of enzymatic activity, respectively.Journal of Clinical Investigation, 1991
- Rearrangements and point mutations of P450c21 genes are distinguished by five restriction endonuclease haplotypes identified by a new probing strategy in 57 families with congenital adrenal hyperplasia.Journal of Clinical Investigation, 1989
- Prenatal Treatment in Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency: Up-Date 88 of the French Multicentric StudyEndocrine Research, 1989
- Molecular Genetic Analysis of Nonclassic Steroid 21-Hydroxylase Deficiency Associated with HLA-B14,DR1New England Journal of Medicine, 1988
- Nonsense mutation causing steroid 21-hydroxylase deficiency.Journal of Clinical Investigation, 1988