title: Novel missense mutations, GCC [Ala306]- > GTC [Val] and ACG [Thr318]- > CCG [Pro], in the CYP11B1 gene cause steroid 11beta-hydroxylase deficiency in the Chinese.
abstract: OBJECTIVE
  Steroid 11beta-hydroxylase (CYP11B1) deficiency, an autosomal recessive inherited disease, accounts for 5-8% of congenital adrenal hyperplasia (CAH). It is mainly caused by mutations of nucleotide substitutions in the coding region.
  
  
  METHODS
  The study reports on a 9-year-old Chinese boy who presented with a bone age of 16 years, an enlarged penis, an accelerated growth rate since early childhood and hypertension (160-170/100-110 mmHg) for 3 years. Because it shares 95% sequence homology with aldosterone synthetase (CYP11B2), we developed gene-specific primers for differential PCR amplification of the CYP11B1 gene. The secondary PCR products of nine exons of the CYP11B1 gene were then subjected to single-strand conformation polymorphism (SSCP) analysis and DNA sequencing. The serum hormone levels were also determined.
  
  
  RESULTS
  We found that the boy diagnosed with CAH due to 11beta-hydroxylase deficiency carried mutations of A306V (GCC- > GTC) and T318P (ACG- > CCG) in two respective chromosomes. The hormone assay showed that the 11-deoxycortisol level was higher (667 nmol/l) than normal and was further increased after ACTH stimulation (1206 nmol/l).
  
  
  CONCLUSIONS
  These two mutations have not previously been described in the CYP11B1 gene. The discovery of these two novel mutations increases our knowledge of CAH caused by 11beta-hydroxylase deficiency.
authors.affiliation: Department of Medical Research, Mackay Memorial Hospital, 45 Min-Sheng Road., Tanshui, Taipei 251, Taiwan. hhlee@msl.mmh.org.tw
authors.forename: Hsien-Hsiung
authors.initials: HH
authors.lastname: Lee
authors.forename: Ging-Shing
authors.initials: GS
authors.lastname: Won
authors.forename: Hsiang-Tai
authors.initials: HT
authors.lastname: Chao
authors.forename: Yann-Jinn
authors.initials: YJ
authors.lastname: Lee
authors.forename: Bon-Chu
authors.initials: BC
authors.lastname: Chung
mesh_terms: D000312:Adrenal Hyperplasia, Congenital / Q000097:blood / Q000208:ethnology / Q000235:genetics*; D000483:Alleles; D002648:Child; D002681:China; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D018807:Polymorphism, Single-Stranded Conformational; D017422:Sequence Analysis, DNA; D013252:Steroid 11-beta-Hydroxylase / Q000097:blood / Q000235:genetics*
chemical_list: D013252:Steroid 11-beta-Hydroxylase