Clinical, genetic and functional characteristics of three novel CYP17A1 mutations causing combined 17α-hydroxylase/17,20-lyase deficiency

Hormone Research in Paediatrics

Volumn 73, Issue 3, 2010, Pages 198-204

  Rosa, S ^a   Steigert, M ^a   Lang Muritano, M ^a   L'Allemand, D ^a   Schoenle, E J ^a   Biason Lauber, A ^a  

^a UNIVERSITY CHILDREN S HOSPITAL   (Switzerland)

Author keywords

Adrenal gland; Intersex; Mutation analysis; P450c17; Steroidogenesis

Indexed keywords

16ALPHA CYANOPREGNENOLONE; ANDROSTENEDIONE; CORTICOSTERONE; CORTICOTROPIN; CYTOCHROME P450 17; CYTOCHROME P450 17A1; CYTOCHROME P450C17; DEOXYCORTICOSTERONE; ESTRADIOL; HYDROCORTISONE; MUTANT PROTEIN; PRASTERONE; PROGESTERONE; SPIRONOLACTONE; STEROID 17,20 LYASE; STEROID 17ALPHA MONOOXYGENASE; TESTOSTERONE; UNCLASSIFIED DRUG;

17,20 LYASE DEFICIENCY; ADD ON THERAPY; ADOLESCENT; ARTICLE; BONE AGE; CASE REPORT; CELL STRAIN COS1; CLITORIS; CORTICOTROPIN BLOOD LEVEL; CRYPTORCHISM; DEPRESSION; DIAGNOSTIC ERROR; DISEASE SEVERITY; DRUG OVERDOSE; DRUG TREATMENT FAILURE; DRUG WITHDRAWAL; ENZYME ACTIVITY; ENZYME DEFICIENCY; FEMALE; GENDER IDENTITY; GENE EXPRESSION; GENE IDENTIFICATION; GENE LOCATION; GENE MUTATION; GENE SEQUENCE; GENITAL MALFORMATION; GENOTYPE PHENOTYPE CORRELATION; GONAD DEVELOPMENT; HEADACHE; HORMONAL REGULATION; HORMONE SUBSTITUTION; HORMONE URINE LEVEL; HUMAN; HYPERTENSION; HYPOKALEMIA; INFANT; KARYOTYPE 46,XY; MASCULINITY; PENIS; PHENOTYPE; PRIORITY JOURNAL; PUBERTY; SEQUENCE ANALYSIS; STEROID 17ALPHA MONOOXYGENASE DEFICIENCY; STRUCTURE ACTIVITY RELATION;

ADRENAL HYPERPLASIA, CONGENITAL; ANIMALS; CERCOPITHECUS AETHIOPS; COS CELLS; FEMALE; GENETIC ASSOCIATION STUDIES; GONADAL DYSGENESIS, 46,XY; HUMANS; INFANT; MALE; MUTATION; STEROID 17-ALPHA-HYDROXYLASE;

EID: 77951284413     PISSN: 16632818     EISSN: 16632826     Source Type: Journal    
DOI: 10.1159/000284362     Document Type: Article

References (14)

1. Picado-Leonard J, Miller WL: Cloning and sequence of the human gene for P450c17 (steroid- -hydroxylase/17,20 lyase): similarity with the gene for P450c21. DNA 1987; 6: 439-448.
2. Biglieri EG, Herron MA, Brust N: 17-Hydroxylation deficiency in man. Clin Invest 1966; 45: 1946-1954.
3. New MI: Male pseudohermaphroditism due to 17-hydroxylase deficiency. Clin Invest 1970; 49: 1930-1941.
4. Miller WL: Steroid 17 -hydroxylase deficiency - not rare everywhere. J Clin Endocrinol Metab 2004; 89: 40-42.
5. Miller WL: Androgen synthesis in adrenarche. Rev Endocr Metab Disord 2009; 10: 3-17.
6. Biason-Lauber A, Leiberman E, Zachmann M: A single amino acid substitution in the putative redox partner-binding site of P450c17 as cause of isolated 17,20-lyase deficiency. J Clin Endocrinol Metab 1997; 82: 3807-3812. (Pubitemid 27509376)
7. Rosa S, Meyer M, Lang-Muritano M, Balercia G, Boscaro M, Kemal Topaloglu A, Mioni R, Fallo F, Zuliani L, Mantero F, Schoenle EJ, Biason-Lauber A: P450c17 deficiency: clinical and molecular characterization of six patients. J Clin Endocrinol Metab 2007; 92: 1000-1007. (Pubitemid 46465675)
8. Fardella CE, Hum DW, Homoki J, Miller WL: Point mutation of Arg440 to His in cytochrome P450c17 causes severe 17 -hydroxylase deficiency. J Clin Endocrinol Metab 1994; 79: 160-164.
9. Speiser PW, Dupont J, Zhu D, et al.: Disease expression and molecular genotype in congenital adrenal hyperplasia due to 21-hydroxylase deficiency. J Clin Invest 1992; 90: 584-595.
10. Auchus RJ, Miller WL: Molecular modeling of human P450c17 (17 -hydroxylase/17,20-lyase): insights into reaction mechanisms and effects of mutations. Mol Endocrinol 1999; 13: 1169-1182.
11. Mathieu AP, Auchus RJ, LeHoux JG: Comparison of the hamster and human adrenal P450c17 (17 -hydroxylase/17,20-lyase) using site-directed mutagenesis and molecular modeling. J Steroid Biochem Mol Biol 2002; 80: 99-107.
12. Geller DH, Auchus RJ, Miller WL: P450c17 mutations R347H and R358Q selectively disrupt 17,20-lyase activity by disrupting interactions with P450 oxidoreductase and cytochrome b5. Mol Endocrinol 1999; 13: 167-175.
13. Lin D, Zhang LH, Chiao E, Miller WL: Modeling and mutagenesis of the active site of human P450c17. Mol Endocrinol 1994; 8: 392-402. (Pubitemid 24108366)
14. Wudy SA, Homoki J: Profiling steroids by gas chromatography-mass spectrometry: clinical applications; in Ranke MB (ed): Diagnostic of Endocrine Function in Children and Adolescents. Basel, Karger, 2003, pp 427-449.