The genetics of steroid 21-hydroxylase deficiency

Endocrinologist

Volumn 15, Issue 1, 2005, Pages 37-43

  Speiser, Phyllis W ^a,b,c  

^a SCHNEIDER CHILDREN'S HOSPITAL   (United States)

^b NEW YORK UNIVERSITY SCHOOL OF MEDICINE   (United States)

^c PFIZER INC   (United States)

Author keywords

Adrenal hyperplasia; Congenital; CYP21; CYP21A2; Genotype; Steroid 21 hydroxylase (monooxygenase)

Indexed keywords

ADRENAL CORTEX; ADRENAL INSUFFICIENCY; ALLELE; AUTOSOMAL RECESSIVE INHERITANCE; BASE PAIRING; CHROMOSOME 6; CONGENITAL ADRENAL HYPERPLASIA; EXON; GENE CONTROL; GENE DELETION; GENE LOCUS; GENITAL MALFORMATION; GENOTYPE; GENOTYPE PHENOTYPE CORRELATION; HISTOCOMPATIBILITY COMPLEX; HUMAN; MISSENSE MUTATION; MUTATION; NEWBORN SCREENING; NONSENSE MUTATION; NUCLEOTIDE SEQUENCE; PHENOTYPIC VARIATION; PRENATAL DIAGNOSIS; REVIEW; SALT LOSING NEPHRITIS; STEROID 21 MONOOXYGENASE DEFICIENCY; VIRILIZATION; ZONA FASCICULATA;

EID: 13144254203     PISSN: 10512144     EISSN: None     Source Type: Journal    
DOI: 10.1097/01.ten.0000152721.30198.08     Document Type: Review

References (64)

1. White PC, Speiser PW. Congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Endocr Rev. 2000;21:245-291.
2. Pang S. Newborn screening for congenital adrenal hyperplasia. Pediatr Ann. 2003;32:516-523.
3. Therrell BL Jr, Berenbaum SA, Manter-Kapanke V, et al. Results of screening 1.9 million Texas newborns for 21-hydroxylase-deficient congenital adrenal hyperplasia. Pediatrics. 1998;101(4 pt 1):583-590.
4. Fitness J, Dixit N, Webster D, et al. Genotyping of CYP21, linked chromosome 6p markers, and a sex-specific gene in neonatal screening for congenital adrenal hyperplasia. J Clin Endocrinol Metab. 1999;84:960-966.
5. Azziz R. Nonclassic adrenal hyperplasia. Curr Ther Endocrinol Metab. 1997;6:175-178.
6. Clayton PE, Miller WL, Oberfield SE, et al. Consensus statement on 21-hydroxylase deficiency from the Lawson Wilkins Pediatric Endocrine Society and the European Society for Pediatric Endocrinology. J Clin Endocrinol Metab. 2002;87:4048-4053.
7. Wilson RC, Mercado AB, Cheng KC, et al. Steroid 21-hydroxylase deficiency: genotype may not predict phenotype. J Clin Endocrinol Metab. 1995;80:2322-2329.
8. Azziz R, Hincapie LA, Knochenhauer ES, et al. Screening for 21-hydroxylase-deficient nonclassic adrenal hyperplasia among hyperandrogenic women: a prospective study. Fertil Steril. 1999;72:915-925.
9. Therrell BL. Newborn screening for congenital adrenal hyperplasia. Endocrinol Metab Clin North Am. 2001;30:15-30.
10. White PC, New MI, Dupont B. HLA-linked congenital adrenal hyperplasia results from a defective gene encoding a cytochrome P-450 specific for steroid 21-hydroxylation. Proc Natl Acad Sci U S A. 1984;81:7505-7509.
11. Pollack MS, Maurer D, Levine LS, et al. HLA typing of amniotic cells: the prenatal diagnosis of congenital adrenal hyperplasia (21-OH-deficiency type). Transplant Proc. 1979;11:1726-1728.
12. White PC, Grossberger D, Onufer BJ, et al. Two genes encoding steroid 21-hydroxylase are located near the genes encoding the fourth component of complement in man. Proc Natl Acad Sci U S A. 1985;82:1089-1093.
13. Bristow J, Tee MK, Gitelman SE, et al. Tenascin-X: a novel extracellular matrix protein encoded by the human XB gene overlapping P450c21B. J Cell Biol. 1993;122:265-278.
14. Schalkwijk J, Zweers MC, Steijlen PM, et al. A recessive form of the Ehlers-Danlos syndrome caused by tenascin-X deficiency. N Engl J Med. 2001;345:1167-1175.
15. Burch GH, Gong Y, Liu W, et al. Tenascin-X deficiency is associated with Ehlers-Danlos syndrome. Nat Genet. 1997;17:104-108.
16. Koppens PF, Hoogenboezem T, Degenhart HJ. Carriership of a defective tenascin-X gene in steroid 21-hydroxylase deficiency patients: TNXB-TNXA hybrids in apparent large-scale gene conversions. Hum Mol Genet. 2002;11:2581-2590.
17. Cargill M, Altshuler D, Ireland J, et al. Characterization of single-nucleotide polymorphisms in coding regions of human genes. Nat Genet. 1999;22:231-238.
18. Tusie Luna MT, White PC. Gene conversions and unequal crossovers between CYP21 (steroid 21-hydroxylase gene) and CYP21P involve different mechanisms. Proc Natl Acad Sci U S A. 1995;92:10796-10800.
19. 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.
20. Bird IM, Mason JI, Rainey WE. Protein kinase A, protein kinase C, and Ca(2+)-regulated expression of 21-hydroxylase cytochrome P450 in H295R human adrenocortical cells. J Clin Endocrinol Metab. 1998;83:1592-1597.
21. Endoh A, Yang L, Hornsby PJ. CYP21 pseudogene transcripts are much less abundant than those from the active gene in normal human adrenocortical cells under various conditions in culture. Mol Cell Endocrinol. 1998;137:13-19.
22. Chang SF, Chung BC. Difference in transcriptional activity of two homologous CYP21A genes. Mol Endocrinol. 1995;9:1330-1336.
23. Chin KK, Chang SF. The -104G nucleotide of the human CYP21 gene is important for CYP21 transcription activity and protein interaction. Nucleic Acids Res. 1998;26:1959-1964.
24. Wijesuriya SD, Zhang G, Dardis A, et al. Transcriptional regulatory elements of the human gene for cytochrome P450c21 (steroid 21-hydroxylase) lie within intron 35 of the linked C4B gene. J Biol Chem. 1999;274:38097-38106.
25. Ozisik G, Achermann JC, Meeks JJ, et al. SF1 in the development of the adrenal gland and gonads. Horm Res. 2003;59(suppl 1):94-98.
26. Zhang Y, Dufau ML. Gene silencing by nuclear orphan receptors. Vitam Horm. 2004;68:1-48.
27. Higashi Y, Yoshioka H, Yamane M, et al. Complete nucleotide sequence of two steroid 21-hydroxylase genes tandemly arranged in human chromosome: a pseudogene and a genuine gene. Proc Natl Acad Sci U S A. 1986;83:2841-2845.
28. White PC, New MI, Dupont B. Structure of human steroid 21-hydroxylase genes. Proc Natl Acad Sci U S A. 1986;83:5111-5115.
29. Harada F, Kimura A, Iwanaga T, et al. Gene conversion-like events cause steroid 21-hydroxylase deficiency in congenital adrenal hyperplasia. Proc Natl Acad Sci U S A. 1987;84:8091-8094.
30. Higashi Y, Tanae A, Inoue H, et al. Aberrant splicing and missense mutations cause steroid 21-hydroxylase [P-450(C21)] deficiency in humans: possible gene conversion products. Proc Natl Acad Sci U S A. 1988;85:7486-7490.
31. White PC, Vitek A, Dupont B, et al. Characterization of frequent deletions causing steroid 21-hydroxylase deficiency. Proc Natl Acad Sci U S A. 1988;85:4436-4440.
32. Collier S, Sinnott PJ, Dyer PA, et al. Pulsed field gel electrophoresis identifies a high degree of variability in the number of tandem 21-hydroxylase and complement C4 gene repeats in 21-hydroxylase deficiency haplotypes. EMBO J. 1989;8:1393-1402.
33. Shen L, Wu LC, Sanlioglu S, et al. Structure and genetics of the partially duplicated gene RP located immediately upstream of the complement C4A and the C4B genes in the HLA class III region: molecular cloning, exon-intron structure, composite retroposon, and breakpoint of gene duplication. J Biol Chem. 1994;269:8466-8476.
34. Lopez-Gutierrez AU, Riba L, Ordonez-Sanchez ML, et al. Uniparental disomy for chromosome 6 results in steroid 21-hydroxylase deficiency: evidence of different genetic mechanisms involved in the production of the disease. J Med Genet. 1998;35:1014-1019.
35. Carrera P, Ferrari M, Beccaro F, et al. Molecular characterization of 21-hydroxylase deficiency in 70 Italian families. Hum Hered. 1993;43:190-196.
36. Higashi Y, Hiromasa T, Tanae A, et al. Effects of individual mutations in the P-450(C21) pseudogene on the P-450(C21) activity and their distribution in the patient genomes of congenital steroid 21-hydroxylase deficiency. J Biochem (Tokyo). 1991;109:638-644.
37. Jaaskelainen J, Levo A, Voutilainen R, et al. Population-wide evaluation of disease manifestation in relation to molecular genotype in steroid 21-hydroxylase (CYP21) deficiency: good correlation in a well defined population. J Clin Endocrinol Metab. 1997;82:3293-3297.
38. Kharrat M, Tardy V, M'Rad R, et al. Molecular genetic analysis of Tunisian patients with a classic form of 21-hydroxylase deficiency: identification of four novel mutations and high prevalence of Q318X mutation. J Clin Endocrinol Metab. 2004;89:368-374.
39. Krone N, Braun A, Roscher AA, et al. Predicting phenotype in steroid 21-hydroxylase deficiency? comprehensive genotyping in 155 unrelated, well defined patients from southern Germany. J Clin Endocrinol Metab. 2000;85:1059-1065.
40. Mornet E, Crete P, Kuttenn F, et al. Distribution of deletions and seven point mutations on CYP21B genes in three clinical forms of steroid 21-hydroxylase deficiency. Am J Hum Genet. 1991;48:79-88.
41. Wedell A, Thilen A, Ritzen EM, et al. Mutational spectrum of the steroid 21-hydroxylase gene in Sweden: implications for genetic diagnosis and association with disease manifestation. J Clin Endocrinol Metab. 1994;78:1145-1152.
42. Dolzan V, Stopar-Obreza M, Zerjav-Tansek M, et al. Mutational spectrum of congenital adrenal hyperplasia in Slovenian patients: a novel Ala15Thr mutation and Pro30Leu within a larger gene conversion associated with a severe form of the disease. Eur J Endocrinol. 2003;149:137-144.
43. Kotaska K, Prusa R. Frequency of CYP21 gene mutations in Czech patients with steroid 21-hydroxylase deficiency and statistical comparison with other populations. Med Princ Pract. 2003;12:243-247.
44. Lobato MN, Ordonez-Sanchez ML, Tusie-Luna MT, et al. Mutation analysis in patients with congenital adrenal hyperplasia in the Spanish population: identification of putative novel steroid 21- hydroxylase deficiency alleles associated with the classic form of the disease. Hum Hered. 1999;49:169-175.
45. Ordonez-Sanchez ML, Ramirez-Jimenez S, Lopez-Gutierrez AU, et al. Molecular genetic analysis of patients carrying steroid 21-hydroxylase deficiency in the Mexican population: identification of possible new mutations and high prevalence of apparent germ-line mutations. Hum Genet. 1998;102:170-177.
46. Tukel T, Uyguner O, Wei JQ, et al. A novel semiquantitative polymerase chain reaction/enzyme digestion-based method for detection of large scale deletions/conversions of the CYP21 gene and mutation screening in Turkish families with 21-hydroxylase deficiency. J Clin Endocrinol Metab. 2003;88:5893-5897.
47. The human gene mutation database. Available at: http://archive.uwcm. ac.uk/uwcm/mg/search/120605.html. 2004.
48. Amor M, Parker KL, Globerman H, et al. Mutation in the CYP21B gene (Ile-172 - Asn) causes steroid 21-hydroxylase deficiency. Proc Natl Acad Sci U S A. 1988;85:1600-1604.
49. Tusie-Luna MT, Traktman P, White PC. Determination of functional effects of mutations in the steroid 21- hydroxylase gene (CYP21) using recombinant vaccinia virus. J Biol Chem. 1990;265:20916-20922.
50. Tusie-Luna MT, Speiser PW, Dumic M, et al. A mutation (Pro-30 to Leu) in CYP21 represents a potential nonclassic steroid 21-hydroxylase deficiency allele. Mol Endocrinol. 1991;5:685-692.
51. Speiser PW, New MI, White PC. Molecular genetic analysis of nonclassic steroid 21-hydroxylase deficiency associated with HLA-B14, DR1. N Engl J Med. 1988;319:19-23.
52. Dipple KM, McCabe ER. Phenotypes of patients with "simple" Mendelian disorders are complex traits: thresholds, modifiers, and systems dynamics. Am J Hum Genet. 2000;66:1729-1735.
53. Scriver CR, Waters PJ. Monogenic traits are not simple: lessons from phenylketonuria. Trends Genet. 1999;15:267-272.
54. Stevens A, Ray DW, Zeggini E, et al. Glucocorticoid sensitivity is determined by a specific glucocorticoid receptor haplotype. J Clin Endocrinol Metab. 2004;89:892-897.
55. Peter M, Sippell WG, Lorenzen F, et al. Improved test to identify heterozygotes for congenital adrenal hyperplasia without index case examination. Lancet. 1990;335:1296-1299.
56. Knochenhauer ES, Cortet-Rudelli C, Cunnigham RD, et al. Carriers of 21-hydroxylase deficiency are not at increased risk for hyperandrogenism. J Clin Endocrinol Metab. 1997;82:479-485.
57. Day DJ, Speiser PW, Schulze E, et al. Identification of non-amplifying CYP21 genes when using PCR-based diagnosis of 21-hydroxylase deficiency in congenital adrenal hyperplasia (CAH) affected pedigrees. Hum Mol Genet. 1996;5:2039-2048.
58. Koppens PF, Hoogenboezem T, Degenhart HJ. Duplication of the CYP21A2 gene complicates mutation analysis of steroid 21-hydroxylase deficiency: characteristics of three unusual haplotypes. Hum Genet. 2002;111:405-410.
59. Dhallan R, Au WC, Mattagajasingh S, et al. Methods to increase the percentage of free fetal DNA recovered from the maternal circulation. JAMA. 2004;291:1114-1119.
60. New MI, Carlson A, Obeid J, et al. Prenatal diagnosis for congenital adrenal hyperplasia in 532 pregnancies. J Clin Endocrinol Metab. 2001;86:5651-5657.
61. Nordenstrom A, Thilen A, Hagenfeldt L, et al. Genotyping is a valuable diagnostic complement to neonatal screening for congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency. J Clin Endocrinol Metab. 1999;84:1505-1509.
62. Barbat B, Bogyo A, Raux-Demay MC, et al. Screening of CYP21 gene mutations in 129 French patients affected by steroid 21-hydroxylase deficiency. Hum Mutat. 1995;5:126-130.
63. Wilson RC, Wei JQ, Cheng KC, et al. Rapid deoxyribonucleic acid analysis by allele-specific polymerase chain reaction for detection of mutations in the steroid 21-hydroxylase gene. J Clin Endocrinol Metab. 1995;80:1635-1640.
64. Speiser PW, White PC. Congenital adrenal hyperplasia. N Engl J Med. 2003;349:776-788.