title: 17alpha-hydroxylase deficiency : biochemical and molecular findings in two sisters and their family.
abstract: OBJECTIVE
  To search for molecular changes in two Argentinian sisters with a clinical and biochemical diagnosis of 17alpha-hydroxylase deficiency.
  
  
  METHODS
  Both patients had 46 XX karyotype, with sexual infantilism, primary amenorrhea, and hypertension. Other member of the first degree family did not have this deficiency. HORMONAL RESULTS: The patients showed high levels of gonadotrophins and progesterone along with very low cortisol and androgen levels. Basal levels of corticosterone were very high, but aldosterone was normal. Both steroids had a high response after adrenocorticotropic hormone (ACTH) stimulation, with no changes in 17-hydroxyl progesterone and cortisol levels. Progesterone, corticosterone, and aldosterone decreased with the dexamethasone test, without modifications in 17-hydroxyl progesterone and cortisol levels. A corticosterone/aldosterone ratio was calculated from the results of the stimulation test; the ratios were similar in both patients. On administration of the ACTH test, both parents and one sister (S2) showed a marked response in corticosterone levels, their corticosterone/aldosterone ratios were also similar to each other and similar to the patients. MOLECULAR RESULTS: Molecular studies in the cytochrome P450 17 (CYP17) gene showed that exon 8 had a 4 bp duplication at codon 480 (CATC) in the two patients and their mother and in exon 1, a C to T transition at codon 96 was identified, changing CGG into TGG in the two patients, S2, and their father.
  
  
  CONCLUSIONS
  Both patients were shown to be compound heterozygous, carrying different alleles in exon 1 and exon 8, inherited from their father and mother, respectively. The molecular results obtained on S2 confirmed the heterozygosity suggested by the stimulated hormonal test and corticosterone/aldosterone ratio.
authors.affiliation: Laboratory of Molecular Biology, Department of Genetic and Molecular Biology, School of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina.
authors.forename: Maria S
authors.initials: MS
authors.lastname: Perez
authors.forename: Haydee
authors.initials: H
authors.lastname: Benencia
authors.forename: Gustavo D
authors.initials: GD
authors.lastname: Frechtel
authors.forename: Eduardo O
authors.initials: EO
authors.lastname: Esteban
authors.forename: Maria Christina
authors.initials: MC
authors.lastname: Gil
authors.forename: Héctor M
authors.initials: HM
authors.lastname: Targovnik
authors.forename: Norma B
authors.initials: NB
authors.lastname: Marquez
mesh_terms: D000312:Adrenal Hyperplasia, Congenital / Q000175:diagnosis* / Q000378:metabolism; D000450:Aldosterone / Q000097:blood; D000595:Amino Acid Sequence; D001483:Base Sequence; D003345:Corticosterone / Q000097:blood; D005091:Exons; D005260:Female; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics*
chemical_list: D000450:Aldosterone; D013254:Steroid 17-alpha-Hydroxylase; D003345:Corticosterone