title: New compound heterozygous mutation in the CYP17 gene in a 46,XY girl with 17 alpha-hydroxylase/17,20-lyase deficiency.
abstract: BACKGROUND
  17alpha-Hydroxylase/17,20-lyase deficiency is caused by a defect of P450c17 which catalyzes both 17alpha-hydroxylase and 17,20-lyase reactions in adrenal glands and gonads.
  
  
  RESULTS
  In the present study, we analyzed the CYP17 gene in a Japanese patient with 17alpha-hydroxylase/17,20-lyase deficiency. The patient was a phenotypic girl and referred to us for right-sided inguinal hernia at the age of 4 years. Biopsy of the herniated gonad showed testicular tissue. The karyotype was 46,XY. At 6 years of age, hypertension was clearly recognized and the patient was diagnosed as having 17alpha-hydroxylase/17,20-lyase deficiency based on the clinical and laboratory findings. Analysis of the CYP17 gene revealed a compound heterozygous mutation. One mutation was an undescribed single nucleotide deletion at codon 247 in exon 4 (CTT to CT: 247delT) and the other was a missense mutation resulting in a substitution of His to Leu at codon 373 in exon 6 (CAC to CTC: H373L), which has been previously shown to abolish both 17alpha-hydroxylase and 17,20-lyase activities. The functional expression study of the 247delT mutant showed that this 247delT mutation completely eliminates both 17alpha-hydroxylase and 17,20-lyase activities.
  
  
  CONCLUSIONS
  Together, these results indicate that the patient is a compound heterozygote for the mutation of the CYP17 gene (247delT and H373L) and that these mutations inactivate both 17alpha-hydroxylase and 17,20-lyase activities and give rise to clinically manifest 17alpha-hydroxylase/17,20-lyase deficiency.
authors.affiliation: Department of Endocrinology and Metabolism, National Children's Medical Research Center, 3-35-31 Taishido, Setagaya-ku, Tokyo 154-8509, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Katsumata
authors.forename: M
authors.initials: M
authors.lastname: Satoh
authors.forename: A
authors.initials: A
authors.lastname: Mikami
authors.forename: S
authors.initials: S
authors.lastname: Mikami
authors.forename: A
authors.initials: A
authors.lastname: Nagashima-Miyokawa
authors.forename: N
authors.initials: N
authors.lastname: Sato
authors.forename: S
authors.initials: S
authors.lastname: Yokoya
authors.forename: T
authors.initials: T
authors.lastname: Tanaka
mesh_terms: D000312:Adrenal Hyperplasia, Congenital; D000818:Animals; D019556:COS Cells; D002460:Cell Line; D002675:Child, Preschool; D004252:DNA Mutational Analysis / Q000379:methods; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics; D006580:Genetic Carrier Screening; D006061:Gonadal Dysgenesis, 46,XY / Q000201:enzymology* / Q000235:genetics*; D006801:Humans; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D013254:Steroid 17-alpha-Hydroxylase / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D013254:Steroid 17-alpha-Hydroxylase