title: Homozygous CYP17A1 mutation (H373L) identified in a 46,XX female with combined 17α-hydroxylase/17,20-lyase deficiency.
abstract: BACKGROUND
  Defects in cytochrome P450c17 are uncommon forms of congenital adrenal hyperplasia caused by CYP17A1 mutations. An H373L mutation in the CYP17A1 gene has been identified in Japanese and Chinese patients. This mutation impairs 17α-hydroxylase and 17,20-lyase activity.
  
  
  METHODS
  A 23-year-old Korean female (46,XX) presented with absent spontaneous puberty and hypertension. Hormonal findings were consistent with combined 17α-hydroxylase/17,20-lyase deficiency. Very high levels of progesterone and 11-deoxycorticosterone were detected, coincident with normal 17-hydroxysteroid levels. Plasma levels of dehydroepiandrosterone, androstenedione and testosterone were extremely low. Mutation analysis of the CYP17A1 gene identified a homozygous missense mutation changing His (CAC) to Leu (CTC) at codon 373. This mutation is known to completely abolish both 17α-hydroxylase and 17,20-lyase activity. The patient's nonconsanguineous parents were heterozygous for this mutation. Of note, her serum steroid levels indicated decreased, but still present, 17α-hydroxylase activity in vivo.
  
  
  CONCLUSIONS
  We detected a homozygous H373L mutation in a patient with combined 17α-hydroxylase/17,20-lyase deficiency. Our findings demonstrate minimally preserved 17α-hydroxylase activity in vivo and contribute to our knowledge of the regional prevalence of this mutation in Northeast Asia.
authors.affiliation: Department of Obstetrics and Gynecology, CHA Bundang Medical Center, CHA University, Gyeonggi do, Korea. yeegen@cha.ac.kr
authors.forename: Mee-Hwa
authors.initials: MH
authors.lastname: Lee
authors.forename: Seok
authors.initials: S
authors.lastname: Won Park
authors.forename: Tae Ki
authors.initials: TK
authors.lastname: Yoon
authors.forename: Sung Han
authors.initials: SH
authors.lastname: Shim
mesh_terms: D058489:46, XX Disorders of Sex Development / Q000150:complications*; D000312:Adrenal Hyperplasia, Congenital / Q000150:complications / Q000201:enzymology / Q000235:genetics*; D000328:Adult; D019943:Amino Acid Substitution; D004252:DNA Mutational Analysis; D005260:Female; D006720:Homozygote; D006801:Humans; D020125:Mutation, Missense; D056910:Republic of Korea; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult
chemical_list: C501892:CYP17A1 protein, human; D013254:Steroid 17-alpha-Hydroxylase