br Acknowledgements DHA was funded by a research grant
Acknowledgements DHA was funded by a research grant from Viamet and IMB and DHA were/are consultants for Viamet/Innocrin. DHA also supported by NIH P51-OD011106.
Introduction Congenital adrenal hyperplasia resulting from 17alpha-hydroxylase and 17,20-lyase deficiency (17OHD) is a rare autosomal recessive disease, caused by mutations in CYP17A1 gene. 17OHD is classified primarily as complete or partial forms. The complete 17OHD is much more common than the partial form , . The complete loss of 17alpha-hydroxylase and 17,20-lyase activity results in a reduction of cortisol and sex hormones, and accumulation of progesterone and 11-deoxycorticosterone (DOC). The compensatory elevation of ACTH secretion leads to adrenal IAA-94 hyperplasia and mineralocorticoid excess, which results in hypertension, hypokalemia and suppression of renin and aldosterone. The defect of sex hormone synthesis results in a female-appearing external genitalia and delayed pubertal development in both sexes. The clinical characteristics in partial 17OHD patients are different from those in complete ones by partial breast development and pubic hair, and oligomenorrhea or secondary amenorrhea in 46,XX patients and ambiguous genitalia in 46,XY patients due to partial deficiency of 17alpha-hydroxylase and 17,20-lyase activity . The CYP17A1 gene consists of eight exons  and is expressed in several steroidogenic tissues, including the adrenal cortex, ovary, and testis. Since the first mutation was identified in a patient with 17OHD in 1988 , more than 100 different mutations have been reported. Those mutations result in either combined or isolated 17alpha-hydroxylase/17,20-lyase enzyme deficiencies . Two large studies have been reported in different ethnical populations including Brazilian and Japanese cohorts. The founder effects were associated with the prevalent 17OHD in those two countries , . However, the relationship between the genotype and phenotype has not been well established in 17OHD patients , , . In our current study, we reported the clinical characteristics and analyzed the CYP17A1 mutations in the second largest cohort of 17OHD patients from a single country. We also explored the relationship of genotype and phenotype in partial and complete 17OHD patients.
Subject and methods
Discussion In the present study, we reported a large cohort of Chinese 17OHD patients, including 1 partial and 25 complete form 23 kindreds. Interestingly, two patients with complete form presented with normal blood pressures. The onset of overt hypertension and hypokalemia could be variously dependent on dietary salt intake and lifestyle . All the patients were treated with glucocorticoids (GCs). Those patients with poorly controlled blood pressure received calcium channel blockers (CCB) or mineralocorticoid receptor antagonist, spironolactone. In our study, the average age for diagnosis was 21 years, which could be due to being neglected by patients’ families. In our study, gene mutation analysis showed that c.985_987delinsAA and c.1460_1469del mutations were prevalent in Chinese 17 OHD patients, accounting for 60.8% and 21.7%, respectively and 82.5% in total. These two mutations in Chinese 17OHD patients was also reported previously , , , . The c.985_987delinsAA mutation was identified in subjects from Korea  and China , , , , meanwhile, the mutation c.1460_1469del was detected in subjects from Thailand  and China , , , . A founder effect of the c.985_987delinsAA and c.1460_1469del mutations should be considered while taking into account of the several migrations from China at the 3rd century BC. This founder effect could be similar to what was reported in Brazilian and Japanese 17OHD patients , . It has been reported that c.985_987delinsAA and c.1460_1469del mutations resulted in a massive reduction of 17alpha-hydroxylase/17,20 lyase activity. The patients with homozygous mutations presented with hypertension and absence of secondary sexual characteristics , , .