White P C, Tusie-Luna M T, New M I, Speiser P W
Division of Pediatric Endocrinology, Cornell University Medical College, New York, New York 10021.
Hum Mutat. 1994;3(4):373-8. doi: 10.1002/humu.1380030408.
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 (P450c21) 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.
遗传性无法合成皮质醇被称为先天性肾上腺增生症。超过90%的病例是由21-羟化酶缺乏引起的。该综合征的特征是雄激素过多的体征，且常伴有盐皮质激素缺乏。类固醇21-羟化酶（P450c21）是一种在肾上腺中表达的微粒体酶，它催化17-羟孕酮和孕酮分别转化为11-脱氧皮质醇和脱氧皮质酮。在人类中，该酶由位于HLA主要组织相容性复合体中的CYP（CYP21B）基因编码，同时还有一个假基因CYP21P（CYP21A）。导致先天性肾上腺增生症的CYP21突变几乎都是由CYP21和CYP21P之间的重组产生的。这些重组要么删除CYP21，要么将有害突变从CYP21P转移到CYP21，这一过程称为表观基因转换。每个突变引起的酶功能损害程度与携带该突变的患者中观察到的缺乏症的临床严重程度相关。
