title: 17alpha-hydroxylase/17,20-Lyase deficiency due to novel compound heterozygote mutations: treatment for tall stature in a female with male pseudohermaphroditism and spontaneous puberty in her affected sister.
abstract: We report on two German sisters with deficiency in the 17alpha-hydroxylase/17,20-lyase enzyme corresponding to typical hormone profile. A paternal nonsense mutation R388X in exon 7 and a maternal missense mutation P428L in exon 8 of the CYP17 gene have been identified in both girls. Residual in vitro 17alpha-hydroxylase activity for the conversion of [3H]-Preg to [3H]-17OH-Preg has been detected in transfected 293-cells expressing P428L mutant enzyme; however, no 17,20-lyase activity was observed converting [3H]-17OH-Preg into [3H]-DHEA. The 46,XX-sister spontaneously entered puberty. The 46,XY-sister with a predicted adult height of 203 cm was treated with a high dose of conjugated estrogens and resulted with a final height of 186.9 cm. The present data suggest that compound heterozygous 46,XX females bearing a P428L allele may develop spontaneous onset of puberty. Furthermore, in 46,XY females with tall stature, treatment with conjugated estrogens may lead to a significant reduction of their predicted adult height.
authors.affiliation: Children's Hospitals of the Universities of Freiburg, Germany. SCHWAB@kikli.ukl.uni-freiburg.de
authors.forename: Karl Otfried
authors.initials: KO
authors.lastname: Schwab
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Moisan
authors.forename: Janos
authors.initials: J
authors.lastname: Homoki
authors.forename: Michael
authors.initials: M
authors.lastname: Peter
authors.forename: Jacques
authors.initials: J
authors.lastname: Simard
mesh_terms: D000293:Adolescent; D000312:Adrenal Hyperplasia, Congenital / Q000150:complications* / Q000235:genetics*; D000328:Adult; D001120:Arginine; D001827:Body Height; D018389:Codon, Nonsense; D012734:Disorders of Sex Development / Q000150:complications / Q000209:etiology / Q000628:therapy*; D004967:Estrogens / Q000627:therapeutic use; D004966:Estrogens, Conjugated (USP) / Q000627:therapeutic use; D005260:Female; D006130:Growth Disorders / Q000150:complications / Q000188:drug therapy* / Q000209:etiology; D006579:Heterozygote; D006801:Humans; D007930:Leucine; D009154:Mutation; D020125:Mutation, Missense; D009919:Orchiectomy; D011392:Proline; D011627:Puberty; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics*
chemical_list: D018389:Codon, Nonsense; D004967:Estrogens; D004966:Estrogens, Conjugated (USP); D001120:Arginine; D011392:Proline; D013254:Steroid 17-alpha-Hydroxylase; D007930:Leucine