Mutations in Steroid 21-Hydroxylase (CYP21)

✍ Scribed by Perrin C. White; Maria-Teresa Tusie-Luna; Maria I. New; Phyllis W. Speiser

• Publisher: John Wiley and Sons
• Year: 1994
• Tongue: English
• Weight: 576 KB
• Volume: 3
• Category: Article
• ISSN: 1059-7794
• DOI: 10.1002/humu.1380030408

✦ Synopsis

The inherited inability to synthesize cortisol is termed congenital adrenal hyperplasia. More than 90% of cases are caused by 2 I-hydroxylase deficiency. This syndrome is characterized by signs of androgen excess and often mineralocorticoid deficiency. Steroid 2 1-hydroxylase (P450c2 1) is a microsomal enzyme expressed in the adrenal gland that catalyzes conversion of 17-hydroxyprogesterone and progesterone to 1 1 -deoxycortisol and deoxycorticosterone respectively. In man, this enzyme is encoded by the CYPZl (CYPZIB) gene which is located in the HLA major histocompatibility complex along with a pseudogene, CYP21P fCYP21A). Mutations in CYPZl causing congenital adrenal hyperplasia are almost all generated by recombinations between CYP21 and CYPZlP. These recombinations either delete CYP2l 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.