title: New, recurrent, and prevalent mutations: Clinical and molecular characterization of 26 Chinese patients with 17alpha-hydroxylase/17,20-lyase deficiency.
abstract: BACKGROUND
  Combined 17alpha-hydroxylase/17,20-lyase deficiency (17OHD), caused by mutations in the CYP17A1 gene, is a rare autosomal recessive form of congenital adrenal hyperplasia and characterized by hyporeninemic hypokalemic hypertension, primary amenorrhea and absence of secondary sexual characteristics.
  
  
  METHODS
  Twenty six 17OHD subjects from 23 Chinese families were recruited. The CYP17A1 gene was sequenced and 17alpha-hydroxylase/17,20-lyase enzymatic activities were assessed in vitro.
  
  
  RESULTS
  Eight CYP17A1 mutations were identified in 23 patients. Of eight mutations, c.985_987delinsAA/p.Y329Kfs and c.1460_1469del/p.D487_F489del mutations accounted for 60.8% (28/46) and 21.7% (10/46) of the mutant alleles, respectively. The enzymatic activities for both mutations were completely abolished. We also identified three novel mutations c.971_972insG/p.K325Afx, c.1464_1466delT/p.F489Sfx and c.1386G>T/p.R462S. The enzymatic activities for c.971_972insG/p.K325Afx and c.1464_1466delT/p.F489Sfx mutations were almost completely abolished, whereas the mutation c.1386G>T/p.R462S only resulted in partial reduction of 17alpha-hydroxylase (34.6%) and 17,20 lyase activities (27.0%), which is correlated with the partial 17OHD phenotype in this patient.
  
  
  CONCLUSIONS
  The c.985_987delinsAA/p.Y329Kfs and c.1460_1469del/p.D487_F489del mutations are prevalent in Chinese 17OHD patients. The genetic defects are well correlated with the phenotypes in both complete and partial forms of 17OHD.
authors.affiliation: Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Key Laboratory of Endocrine Tumor, Shanghai Institute of Endocrinology and Metabolism, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Rui Jin 2nd Road, Shanghai 200025, China; Department of Endocrinology & Metabolism, Shanghai Tenth People's Hospital, Tongji University School of Medicine, 301 Middle Yanchang Road, Shanghai 200072, China.
authors.forename: Manna
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Key Laboratory of Endocrine Tumor, Shanghai Institute of Endocrinology and Metabolism, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Rui Jin 2nd Road, Shanghai 200025, China.
authors.forename: Shouyue
authors.initials: S
authors.lastname: Sun
authors.affiliation: Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Key Laboratory of Endocrine Tumor, Shanghai Institute of Endocrinology and Metabolism, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Rui Jin 2nd Road, Shanghai 200025, China.
authors.forename: Yanling
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Key Laboratory of Endocrine Tumor, Shanghai Institute of Endocrinology and Metabolism, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Rui Jin 2nd Road, Shanghai 200025, China.
authors.forename: Huijie
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Key Laboratory of Endocrine Tumor, Shanghai Institute of Endocrinology and Metabolism, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Rui Jin 2nd Road, Shanghai 200025, China; Department of Endocrinology & Metabolism, Shanghai Tenth People's Hospital, Tongji University School of Medicine, 301 Middle Yanchang Road, Shanghai 200072, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Jiao
authors.affiliation: Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Key Laboratory of Endocrine Tumor, Shanghai Institute of Endocrinology and Metabolism, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Rui Jin 2nd Road, Shanghai 200025, China.
authors.forename: Weiqing
authors.initials: W
authors.lastname: Wang
authors.affiliation: Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Key Laboratory of Endocrine Tumor, Shanghai Institute of Endocrinology and Metabolism, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Rui Jin 2nd Road, Shanghai 200025, China. Electronic address: lixy@sibs.ac.cn.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Li
mesh_terms: D000293:Adolescent; D000312:Adrenal Hyperplasia, Congenital / Q000201:enzymology / Q000208:ethnology / Q000235:genetics* / Q000503:physiopathology; D000328:Adult; D000483:Alleles; D044466:Asian People; D001483:Base Sequence; D002648:Child; D004252:DNA Mutational Analysis; D005260:Female; D005808:Genes, Recessive; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D012720:Severity of Illness Index; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics* / Q000378:metabolism
chemical_list: D013254:Steroid 17-alpha-Hydroxylase
keywords: 17Alpha-hydroxylase/17,20-lyase deficiency; CYP17A1 gene; Congenital adrenal hyperplasia; Mutation