[Detection of CYP21A2 gene mutations and the differences in the levels of hormones in patients with 21-hydroxylase deficiency].

To analyze the detection of CYP21A2 gene mutations in 21-hydroxylase deficiency (21-OHD) patients, so as to determine the accuracy of clinical diagnosis. Totally, 514 patients with 21-OHD who visited Peking Union Medical College Hospital from January 2015 to January 2018 were enrolled and their clinical and biochemical data were collected. DNAs were extracted from peripheral blood leukocytes and CYP21A2 mutations were detected by Sanger sequencing and multiple ligation probe amplification (MLPA) technique. We divided 514 patients into three groups: two mutations of CYP21A2 alleles (group A), one mutation of CYP21A2 (group B), and no mutation of CYP21A2 (group C). Mutation was detected in each allele of CYP21A2 gene in 401 (78.0%) patients, ninety (17.5%) had only one mutant allele and 23 (4.5%) had no mutation. There was no significant difference between the patients with different clinical phenotypes and the number of CYP21A2 gene mutations detected. In male, the cortisol of the patients with simple virilizing 21-OHD in group A [0.04 (0.02, 0.20) nmol/L] was lower than that of group B [0.24 (0.17, 0.28) nmol/L] and the difference was statistically significant (0.014). In female, 17-hydroxyprogesterone (17-OHP) of patients with salt wasting 21-OHD in group A [153.7 (90.1, 204.5) nmol/L] was higher than that of group B [38.2 (31.0, 183.3) nmol/L] and C [42.6 (27.8, 48.1) nmol/L] and the differences were statistically significant (both 0.05). The progesterone of patients with simple virilizing 21-OHD in group C [23.0 (8.6, 33.2) nmol/L] was lower than that of gourp A [57.8 (34.4, 110.2) nmol/L] and B [63.6 (31.4, 110.8) nmol/L] and the difference were statistically significant (both 0.05). The 17-OHP of patients with non-classical 21-OHD in group C [24.5 (20.4, 54.2) nmol/L] was lower than that of group A [158.7 (59.1, 187.6) nmol/L] and B [147.8 (131.9, 179.3) nmol/L]. The difference were statistically significant (both 0.05). Mutations of two alleles have not been found in all patients with clinically diagnosed 21-OHD. Other congenital adrenal hyperplasia (CAH) types which can cause similar changes in 17-OHP and other hormones may be misdiagnosed as 21-OHD. Therefore, 21-OHD cannot be diagnosed with help of 17-OHP level only, and gene detection plays a vital role in the differential diagnosis of different CAH types.