Molecular diagnosis of congenital adrenal hyperplasia in Iran: Focusing on CYP21A2 gene

Iranian Journal of Pediatrics

Volumn 21, Issue 2, 2011, Pages 139-150

  Rabbani, Bahareh ^a,b   Mahdieh, Nejat ^c   Ashtiani, Mohammad Taghi Haghi ^b   Akbari, Mohammad Taghi ^d   Rabbani, Ali ^a,b  

^a TEHRAN UNIVERSITY OF MEDICAL SCIENCES   (Iran)

^b TEHRAN UNIVERSITY OF MEDICAL SCIENCES   (Iran)

^c ILAM UNIVERSITY OF MEDICAL SCIENCES   (Iran)

^d TARBIAT MODARES UNIVERSITY   (Iran)

Author keywords

21 hydroxylase deficiency; Congenital adrenal hyperplasia; Iranian population; Molecular genetics

Indexed keywords

3(OR 17)BETA HYDROXYSTEROID DEHYDROGENASE; ALDOSTERONE; ANDROSTENEDIONE; CHOLESTEROL MONOOXYGENASE (SIDE CHAIN CLEAVING); CYTOCHROME P450 21A2; CYTOCHROME P450 REDUCTASE; HYDROCORTISONE; HYDROXYPROGESTERONE; PRASTERONE; STEROID 11BETA MONOOXYGENASE; STEROID 17ALPHA MONOOXYGENASE; STEROID 21 MONOOXYGENASE; TESTOSTERONE; UNCLASSIFIED DRUG;

ACIDOSIS; ACNE; AMBIGUOUS GENITALIA; APPETITE DISORDER; CLINICAL FEATURE; CONGENITAL ADRENAL HYPERPLASIA; CYP21A2 GENE; DEHYDRATION; DIAGNOSTIC ACCURACY; DIARRHEA; FAILURE TO THRIVE; GENE EXPRESSION; GENE FREQUENCY; GENE FUNCTION; GENE IDENTIFICATION; GENE LOCATION; GENE MUTATION; GENETIC COUNSELING; GENOTYPE; HETEROZYGOSITY; HIRSUTISM; HUMAN; INFERTILITY; IRAN; MOLECULAR DIAGNOSIS; OLIGOMENORRHEA; POLYMERASE CHAIN REACTION; PRECOCIOUS PUBERTY; PRENATAL DIAGNOSIS; PREVALENCE; PSEUDOHERMAPHRODITISM; REVIEW; TALL STATURE; VIRILIZATION; VOMITING; WEIGHT REDUCTION;

EID: 79959260498     PISSN: 10184406     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (87)

1. Villee DB. The development of steroidogenesis. Am J Med 1972;53(5):533-44.
2. Williams JS, Williams GH. 50th anniversary of aldosterone. J Clin Endocrinol Metab 2003;88(6): 2364-72.
3. Pang SY, Wallace MA, Hofman L, et al. Worldwide experience in newborn screening for classical congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Pediatrics 1988;81(6): 866-74.
4. White PC. Congenital adrenal hyperplasia. In: Kliegman RM, Behrman RE, Jenson HB, Stanton BF. Nelson Textbook of Pediatrics. 18th ed. Philadelphia: Saunders. 2007; Pp: 2360-68.
5. Forest MG. Recent advances in the diagnosis and management of congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Hum Reprod 2004; 10(6):469-85.
6. Yanase T. 17 alpha-Hydroxylase/17, 20-lyase defects. J Steroid Biochem Mol Biol 1995;53(1-6): 153-7.
7. Yanase T, Simpson ER, Waterman MR. 17 alpha-hydroxylase/17, 20-lyase deficiency: from clinical investigation to molecular definition. Endocr Rev 1991;12(1):91-108.
8. White PC, Curnow KM, Pascoe L. Disorders of steroid 11 beta-hydroxylase isozymes. Endocr Rev 1994;15(4):421-38.
9. Lin D, Sugawara T, Strauss JF, et al. Role of steroidogenic acute regulatory protein in adrenal and gonadal steroidogenesis. Science 1995; 267(5205):1828-31.
10. Peter M, Janzen N, Sander S, et al. A case of 11β-hydroxylase deficiency detected in a newborn screening program by second-tier LC-Ms/Ms. Horm Res 2008;69(4):253-6.
11. Moisan AM, Ricketts ML, Tardy V, et al. New insight into the molecular basis of 3beta-hydroxysteroid dehydrogenase deficiency: identification of eight mutations in the HSD3B2 gene in eleven patients from seven new families and comparison of the functional properties of twenty-five mutant enzymes. J Clin Endocrinol Metab 1999; 84(12): 4410-25.
12. Rabbani A, Goharfar B, Dehgani A. Pseudohypo-aldosteronism. Acta Medica Iranica 1996;34(3):101-103.
13. Moayeri H, Rabbani A. Report of 285 patients with congenital adrenal hyperplasia and evaluation of approximate prevalence of the disease in Iran. Acta Medica Iranica 1999;37(2):102-5.
14. Razzaghy-Azar M, Zangeneh F, Nourbakhsh M. A review of 433 patients with congenital adrenal hyperplasia. Iran J Endocrinol Metab 2002;4(3):184-95.
15. Moayeri H, Rabbani A. Non classic 21 hydroxylase deficient adrenal hyperplasia in patients with isolated precocious pubarche. Acta Medica Iranica 2003;4(3):171-4.
16. Ghazi AA, Hadayegh F, Khakpour G, et al. Bilateral testicular enlargement due to adrenal remnant in a patient with C11 hydroxylase deficiency congenital adrenal hyperplasia. J Endocrinol Invest 2003;26(1): 84-7.
17. Rohani F, Gregorian A. A 10-year review of clinical manifestations and frequency of enzyme defects in patients with CAH in the Institute of Endocrinology and Metabolism. Iran Univ Med Sci 2005;12(47):59-68.
18. Haghi Ashtiani MT, Rabbani A, Mostafavi F, et al. HLA typing of patients with 21-hydroxylase deficiency in Iranian children with congenital adrenal hyperplasia. Biochem Genet 2008;46(11-12):712-9.
19. Mostafavi F, Baghramian A, Madani A, Haghi-Ashtiani MT. Serum 17α-hydroxyprogesterone, 4Δ-androstenedione and cortisol levels in healthy full term neonates. Arch Iran Med 2001;4(3):130-2.
20. Vakili R, Baradaran-Heravi A, Barid-Fatehi B, et al. Molecular analysis of the CYP21 gene and prenatal diagnosis in families with 21-hydroxylase deficiency in northeastern Iran. Horm Res 2005;63(3):119-24.
21. Ramazani A, Kahrizi K, Razaghiazar M, et al. The frequency of eight common point mutations in CYP21 gene in Iranian patients with congenital adrenal hyperplasia. Iran Biomed J 2008;12(1):49-53.
22. White PC. Congenital adrenal hyperplasia. Best Pract Res Clin Endocrinol & Metab 2001;15(1):17-41.
23. White PC, Speiser PW. Congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Endocr Rev 2000;21(3):245-91.
24. Forest MG. Peripubertal hyperandrogenism. Minerva Pediatr 1996;48(5):179-91.
25. Fluck CE, Miller WL. P450 oxidoreductase deficiency: a new form of congenital adrenal hyperplasia. Curr Opin Pediatr 2006;18(4):435-41.
26. Fluck CE, Tajima T, Pandey AV, et al. Mutant P450 oxidoreductase causes disordered steroidgenesis with and without Antley-Bixler syndrome. Nat Genet 2004;36(3):228-30.
27. Fluck CE, Miller WL, Auchus RJ. The 17, 20-lyase activity of cytochrome p450c17 from human fetal testis favors the delta5 steroidogenic pathway. J Clin Endocrinol Metab 2003;88(8):3762-6.
28. Forest MG. Adrenal function tests. In Ranke MB (ed) Functional endocrinologic diagnostics in children and adolescents. J & J Verlag, Mannheim, 1992; Pp: 248-74.
29. Pang S. Congenital adrenal hyperplasia. Endocrinol Metab Clin North Am 1997;26(4):853-91.
30. Van der Kamp HJ, Wit JM. Neonatal screening for congenital adrenal hyperplasia. Eur J Endocrinol 2004;151(Suppl 3):U71-5.
31. Baumgartner-Parzer SM, Nowotny P, Heinze G, et al. Carrier frequency of congenital adrenal hyperplasia (21-hydroxylase deficiency) in a Middle European population. J Clin Endocrinol Metab 2005;90(2):775-8.
32. 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 USA 1985;82(4):1089-93.
33. White PC, New MI, Dupont B. Adrenal 21-hydroxylase cytochrome P-450 genes within the MHC class III region. Immunol Rev 1985;87:123-50.
34. Goncalves J, Friaes A, Moura L. Congenital adrenal hyperplasia: focus on the molecular basis of 21-hydroxylase deficiency. Expert Rev Mol Med 2007; 9(11):1-23.
35. Morel Y, Bristow J, Gitelman SE, Miller WL. Transcript encoded on the opposite strand of the human steroid 21-hydroxylase/ complement component C4 gene locus. Proc. Natl Acad Sci USA 1989; 86(17):6582-6.
36. 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(1):265-78.
37. Yang Z, Mendoza AR, Welch TR, et al. Modular variations of the human major histocompa-tibility complex class III genes for serine/threonine kinase RP, complement component C4, steroid 21-hydroxylase CYP21, and tenascin TNX (the RCCX module). A mechanism for gene deletions and disease associations. J Biol Chem 1999;274(11):12147- 56.
38. Speiser PW, White PC. Congenital adrenal hyperplasia. N Engl J Med 2003;349(8):776-88.
39. Lee HH. Diversity of the CYP21P-Like Gene in CYP21 Deficiency. DNA & Cell Bio 2005;24(1):1-9.
40. Lee HH. Chimeric CYP21P/CYP21 and TNXA/TNXB genes in the RCCX module. Mol Genet Metab 2005; 84(1):4-8.
41. Lee HH. The chimeric CYP21P/CYP21 gene and 21-hydroxylase deficiency. J Hum Genet 2004; 49(2):65-72.
42. Lee HH, Chao HT, Ng HT, Choo KB. Direct molecular diagnosis of CYP21 mutations in congenital adrenal hyperplasia. J Med Genet 1996;33(5):371-5.
43. Lee HH, Chao HT, Lee YJ, et al. Identification of four novel mutations in the CYP21 gene in congenital adrenal hyperplasia in the Chinese. Hum Genet 1998;103(3):304-10.
44. Ahlgren R, Yanase T, Simpson ER, et al. Compound heterozygous mutations (Arg 239----stop, Pro 342----Thr) in the CYP17 (P45017 alpha) gene lead to ambiguous external genitalia in a male patient with partial combined 17 alpha-hydroxylase/17,20-lyase deficiency. J Clin Endocrinol Metab 1992;74(3):667-72.
45. Asanuma A, Ohura T, Ogawa E, et al. Molecular analysis of Japanese patients with steroid 21-hydroxylase deficiency. J Hum Genet 1999;44(5): 312-7.
46. Friaes A, Rego AT, Aragues JM, et al. CYP21A2 mutations in Portuguese patients with congenital adrenal hyperplasia: identification of two novel mutations and characterization of four different partial gene conversions. Mol Genet Metab 2006; 88(1):58-65.
47. Krone N, Braun A, Weinert S, et al. Multiplex minisequencing of the 21-hydroxylase gene as a rapid strategy to confirm congenital adrenal hyperplasia. Clin Chem 2002;48(6 pt 1):818-25.
48. Wilson RC, Nimkarn S, Dumic M, et al. Ethnic-specific distribution of mutations in 716 patients with congenital adrenal hyperplasia owing to 21-hydroxylase deficiency. Mol Genet Metab 2007; 90(4):414-21.
49. Lee HH, Lee YJ, Wang YM, et al. Low frequency of the CYP21A2 deletion in ethnic Chinese (Taiwanese) patients with 21-hydroxylase deficiency. Mol Genet Metab 2008;93(4):450-7.
50. Sadeghi F, Yurur-Kutlay N, Berberoglu M, et al. Identification of frequency and distribution of the nine most frequent mutations among patients with 21-hydroxylase deficiency in Turkey. J Pediatr Endocrinol Metab 2008;21(8):781-7.
51. Campos VC, Pereira RM, Torres N, et al. High frequency of Q318X mutation in patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency in northeast Brazil. Arq Bras Endocrinol Metabol 2009;53(1):40-6.
52. Araujo RS, Mendonca BB, Barbosa AS, et al. Microconversion between CYP21A2 and CYP21A1P promoter regions causes the nonclassical form of 21-hydroxylase deficiency. J Clin Endocrinol Metab 2007;92(10):4028-44.
53. Chang SH, Lee HH, Wang PJ, et al. Congenital adrenal hyperplasia with 11 beta-hydroxylase deficiency. J Formos Med Assoc 2004;103(11): 860-4.
54. Zhao LQ, Han S, Tian HM. Progress in molecular-genetic studies on congenital adrenal hyperplasia due to 11 beta-hydroxylase deficiency. World J Pediatr 2008;4(2):85-90.
55. Auchus RJ, Gupta MK. Towards a unifying mechanism for CYP17 mutations that cause isolated 17, 20-lyase deficiency. Endoc Res 2002;28(4):443-7.
56. Geller DH, Auchus RJ, Mendonca BB, Miller WL. The genetic and functional basis of isolated 17, 20-lyase deficiency. Nat Genet 1997;17(2):201-5.
57. Wong SL, Shu SG, Tsai CR. Seventeen alpha-hydroxylase deficiency. J Formos Med Assoc 2006; 105(2):177-81.
58. Krone N, Arlt W. Genetics of congenital adrenal hyperplasia. Best Pract Res Clin Endocrinol Metab 2009;23(1):181-92.
59. Pang S. The molecular and clinical spectrum of 3 beta-hydroxysteroid dehydrogenase deficien-cy disorder. Trends Endocrinol Metab 1998;9(2):82-6.
60. Pang S. Congenital adrenal hyperplasia owing to 3 beta-hydroxysteroid dehydrogenase deficiency. Endocrinol Metab Clin North Am 2001;30(1):81-99.
61. Baker BY, Lin L, Kim CJ, et al. Nonclassic congenital lipoid adrenal hyperplasia: a new disorder of the steroidogenic acute regulatory protein with very late presentation and normal male genitalia. J Clin Endocrinol Metab 2006; 91(12):4781-5.
62. Bose HS, Sato S, Aisenberg J, et al. Mutations in the steroidogenic acute regulatory protein (StAR) in six patients with congenital lipoid adrenal hyperplasia. J Clin Endocrinol Metab 2000; 85(10):3636-9.
63. Dacou-Voutetakis C, Maniati-Christidi M, Dracopoulou-Vabouli M. Genetic aspects of congenital adrenal hyperplasia. J Pediatr Endocrinol Metab 2001;14(Suppl 5):1303-8.
64. 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(12):5893-7.
65. Lee HH, Lee YJ, Lin CY. PCR-based detection of the CYP21 deletion and TNXA/TNXB hybrid in the RCCX module. Genomics 2004;83(5):944-50.
66. Kharrat M, Tardy R, 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 Metabo 2006;89(1):368-74.
67. Neocleous V, Ioannou YS, Bartsota M, et al. Rare mutations in the CYP21A2 gene detected in congenital adrenal hyperplasia. Clin Biochem 2009; 42(13-14):1363-7.
68. Concolino P, Mello E, Toscano V, et al. Multiplex ligation-dependent probe amplification (MLPA) assay for the detection of CYP21A2 gene deletions/duplications in congenital adrenal hyperplasia: first technical report. Clin Chim Acta 2009;402(1-2):164-70.
69. Sørensen KM, Andersen PS, Larsen LA, et al. Multiplex Ligation-Dependent Probe Amplification technique for copy number analysis on small amounts of DNA material. Anal Chem 2008;80(23): 9363-8.
70. Olney RC, Mougey EB, Wang J, et al. Using realtime, quantitative PCR for rapid genotyping of the steroid 21-hydroxylase gene in a north Florida population. J Clin Endocrinol Metab 2002;87(2): 735-41.
71. Parajes S, Quinterio C, Dominguez F, Loidi L. A simple and robust quantitative PCR assay to determine CYP21A2 gene dose in the diagnosis of 21-hydroxylase deficiency. Clin Chem 2007;53(9): 1577-84.
72. Ezquieta B, Beneyto M, Mun-Pacheco R, et al. Gene duplications in 21-hydroxylase deficiency: the importance of accurate molecular diagnosis in carrier detection and prenatal diagnosis. Prenat Diagn 2006;26(12):1172-8.
73. Rabbani B, Mahdieh N, Zaridust E, et al. Homozygous complete deletion of CYP21A2 causes a simple virilizing phenotype in an Azeri family. Asian Biomed 2011;DOI 10.5372/1905-7415.0505.042.
74. Baumgartner-Parzer SM, Fischer G, Vierhapper H. Predisposition for de novo gene aberrations in the offspring of mothers with a duplicated CYP21A2 gene. J Clin Endocrinol Metab 2007;92(3):1164-7.
75. Mahdieh N, Rabbani B, Wiley S, et al. Genetic causes of nonsyndromic hearing loss in Iran in comparison with other populations. J Hum Genet 2010;55(10):639-48.
76. Mahdieh N, Rabbani B. Statistical study of 35delG mutation of GJB2 gene: A meta-analysis of carrier frequency. Int J Audiol 2009;48(6):363-70.
77. Nimkarn S, New MI. Prenatal diagnosis and treatment of congenital adrenal hyperplasia. Pediatr Endocrinol Rev 2006;4(2):99-105.
78. Nimkarn S, and New MI. Prenatal diagnosis and treatment of congenital adrenal hyperplasia owing to 21-hydroxylase deficiency. Nat Clin Prac Endocrinol Metab 2007;3(5):405-13.
79. Nimkarn S, New MI. Prenatal Diagnosis and Treatment of Congenital Adrenal Hyperplasia. Horm Res 2007;67(2):53-60.
80. Bhangoo A, Buyuk E, Oktay K, Ten S. Phenotypic features of 46,XX females with StAR protein mutations. Pediatr Endocrinol Rev 2007;5(2):633-41.
81. Miller WL. Disorders of androgen synthesis-from cholesterol to hydroepiandrosterone. Med Princ Pract 2005;14(Suppl 1):58-68.
82. Kaku U, Kameyama K, Izawa M, et al. Ovarian histological findings in an adult patient with the steroidogenic acute regulatory protein (StAR) deficiency reveal the impairment of steroidogenesis by lipoid deposition. Endocr J 2008;55(6):1043-9.
83. Ergun-Longmire B, Auchus R, et al. Two novel mutations found in a patient with 17alpha-hydroxylase enzyme deficiency. J Clin Endocrinol Metab 2006;91(10):4179-82.
84. Yang J, Cui B, Sun S, et al. Phenotype-genotype correlation in eight Chinese 17alpha-hydroxylase/ 17,20 lyase-deficiency patients with five novel mutations of CYP17A1 gene. J Clin Endocrinol Metab 2006;91(9):3619-25.
85. Parajes S, Loidi L, Reisch N, et al. Functional consequences of seven novel mutations in the CYP11B1 gene: four mutations associated with nonclassic and three mutations causing classic 11{beta}-hydroxylase deficiency. J Clin Endocrinol Metab 2010;95(2):779-88.
86. Nimkarn S, New MI. Steroid 11beta-hydroxylase deficiency congenital adrenal hyperplasia. Trends Endocrinol Metab 2008;19(3):96-9.
87. Hauffa BP, Miller WL, Grumbach MM, et al. Congenital adrenal hyperplasia due to deficient cholesterol side-chain cleavage activity (20, 22-desmolase) in a patient treated for 18 years. Clin Endocrinol 1985;23(5):481-93.