title: A prevalent and three novel mutations in CYP11B1 gene identified in Chinese patients with 11-beta hydroxylase deficiency.
abstract: 11β-Hydroxylase deficiency (11β-OHD), caused by CYP11B1 mutations, is characterized by hyporeninemic, hypokalemic hypertension and hyperandrogenism. We identified a prevalent and three novel mutations of CYP11B1 gene in nine patients with classic 11β-OHD.
  
  
  METHODS
  Nine patients with 11β-OHD from unrelated families were recruited. The complications of 11β-OHD occurred in three patients who never received glucocorticoid treatment. CYP11B1 gene was sequenced and 11β-hydroxylase enzymatic activities were assessed in vitro. A haplotype analysis was performed to determine a common ancestor for those subjects who carried the same p.R454C mutation.
  
  
  RESULTS
  CYP11B1 gene mutations were identified in all patients, with a prevalent (p.R454C) and three novel mutations (p.V148G, IVS7-9C>A, c.1359_1360insG). The p.R141X, p.V148G, c.1359_1360insG and p.R454C mutations retained 4.9%, 3.9%, 3.7%, 4.5% of residual enzymatic activity, respectively. Five of nine patients carried p.R454C mutation, which was only reported in Chinese 11OHD patients. Haplotype analysis showed that this mutation might be inherited from a common ancestor.
  
  
  CONCLUSIONS
  The enzymatic activities for p.R141X, p.V148G, c.1359_1360insG and p.R454C mutants were almost completely abolished, which corresponds to classic form of 11β-OHD. The observations of a prevalent mutation and three novel mutations might have potential clinical utility for genetic counseling and prenatal diagnosis in Chinese 11β-OHD patients.
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 RuiJin 2nd Road, Shanghai 200025, China.
authors.forename: Manna
authors.initials: M
authors.lastname: Zhang
authors.forename: Yanling
authors.initials: Y
authors.lastname: Liu
authors.forename: Shouyue
authors.initials: S
authors.lastname: Sun
authors.forename: Huijie
authors.initials: H
authors.lastname: Zhang
authors.forename: Weiqing
authors.initials: W
authors.lastname: Wang
authors.forename: Guang
authors.initials: G
authors.lastname: Ning
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Li
mesh_terms: D000293:Adolescent; D000312:Adrenal Hyperplasia, Congenital / Q000201:enzymology* / Q000235:genetics*; D000328:Adult; D044466:Asian People / Q000235:genetics; D001483:Base Sequence; D002681:China; D004252:DNA Mutational Analysis; D017931:DNA Primers / Q000235:genetics; D005260:Female; D006239:Haplotypes; D006801:Humans; D008297:Male; D009154:Mutation; D013252:Steroid 11-beta-Hydroxylase / Q000097:blood / Q000235:genetics*; D055815:Young Adult
chemical_list: D017931:DNA Primers; D013252:Steroid 11-beta-Hydroxylase