INTRON 2 SPLICE MUTATION AT CYP21 GENE IN PATIENTS WITH CONGENITAL ADRENAL HYPERPLASIA IN THE REPUBLIC OF MACEDONIA
Anastasovska V, Kocova M
*Corresponding Author: Mirjana Kocova, Department of Endocrinology and Genetics, University Children’s Clinic, Vodnjanska 17, 1000 Skopje, Republic of Macedonia; Tel.: +389-70-242-694; Fax: +389-23-129-027; E-mail: mirjanakocova@yahoo.com
page: 27

REFERENCES

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Carrier frequency of congenital adrenal hyperplasia (21-hydroxylase deficiency) in a Middle European population. J Clin Endocrinol Metab 2005; 90(2): 775-778. 8. Strachan T. Molecular patology of 21-hydroxylase deficiency. J Inher Metab Dis 1994; 17(4): 430-441. 9 Fitness J, Dixit N, Webster D, Torresani T, Pergolizzi R, Speiser PW, Day DJ. Genotyping og CYP21, linked chromosome 6p markers, and a sexspecific gene in neonatal screening for congenital adrenal hyperplasia. J Clin Endocrinol Metab 1999; 84(3): 960-966. 10. White PC, Tusie-Luna MT, New MI, Speiser PW. Mutations in steroid 21-hydroxylase (CYP21). Hum Mutat 1994; 3(4): 373-378. 11. Higashi Y, Yoshioka H, Yamane M, Gotoh O, Fujii-Kuriyama Y. Complete nucleotide sequence of two steroid 21-hydroxylase genes tandemly arranged in human chromosome: a pseudogene and a genuine gene. Proc Natl Acad Sci USA 1986; 83(9): 2841-2845. 12. Tusié-Luna MT, White PC. Gene conversion and unequal crossovers between CYP21 (steroid 21-hydroxylase gene) and CYP21P involve different mechanisms. Proc Natl Acad Sci USA 1995; 92(23): 10796-10800. 13. White PC, New MI, Dupont B. Structure of the human steroid 21-hydroxylase gene. Proc Natl Acad Sci USA 1986; 83(14): 5111-5115. 14. Jaaskelainen J, Levo A, Voutilainen R, Partanen J. Population-wide evaluation of disease manifestation in relation to molecular genotype in steroid 21-hydroxylase (CYP21) deficiency: good correlation in well defined population. J Clin Endocrinol Metab 1997; 82(10): 3293-3297. 15. Krone N, Braun A, Rosher AA, Knorr D, Schwarz HP. Predicting phenotype in steroid 21-hydroxylase deficiency? Comprehensive genotyping in 155 unrelated, well defined patients from southern Germany. J Clin Endocrinol Metab 2000; 85(3): 1059-1065. 16. Rosha RO, Billerbeck AEC, Pinto EM, Melo KFS, Lin CJ, Longui CA, Mendoca BB, Bachega TASS. The degree of external genitalia virilization in girls with 21-hydroxylase deficiency appears to be influenced by the CAG repeats in the androghen receptor gene. Clin Endocrinol 2008; 68(2): 226-232. 17. Fardella CE, Poggi H, Pineda P, Soto J, Torrealba I, Cattani A, Oestreicher E, Foradori A. Salt-wasting congenital adrenal hyperplasia: detection of mutations in CYP21B gene in a Chilean population. J Clinic Endocrinol Metab 1998; 83 (9): 3357-3360. 18. Mornet E, Crété P, Kuttenn F, Raux-Demay MCh, Boué J, White PC, Boué A. 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(1): 79-88. 19. Arlt W, Walker EA, Draper N, Ivison HE, Ride JP, Hammer F, Chalder SM, Borucka- Mankiewicz M, Hauffe BP, Malunowicz EM, Stewart PM, Shackleton CHL. Congenital adrenal hyperplasia caused by mutant P450 oxidoreductase and human androgen synthesis: analytical study. Lancet 2004; 363(9427): 2128-2135. 20. Efremov GD, Dimovski AJ, Plaseska- Karanfilska D, Simjanovska L, Sukarova E, Koceva S. Laboratory Manual, 3rd ed. Nucleic Acid Based Methods in Human and Veterinerary Medicine. ICGEB Affiliated Center. Skopje, Republic of Macedonia, 1999. 21. Lee HH, Chao HT, Ng HT, Choo KB. Direct molecular diagnosis of CYP21 mutations in congenital adrenal hyperplasia. J Med Genet 1996; 33(5): 371-375. 22. Wedell A. Molecular genetics of congenital adrenal hyperplasia (21-hydroxylase deficiency): implication for diagnosis, prognosis ant treatment. Acta Pediatr 1998; 87(2): 159-164. 23. Wedell A, Thilen A, Ritzen EM, Stengler B, Luthman H. Mutational spectrum of the steroid 21-hydroxylase gene in Sweden: implications for genetic diagnosis and association with disease manifestations. J Clin Endocrinol Metab 1994; 78(5): 1145-1152. 24. Ramazani A, Kahrizi K, Razaghiazar M, Mahdieh N, Koppens P. 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. 25. Dolžan V, Sólyom J, Fekete G, Kovács J, Rakosnikova V, Voltava F, Lebl J, Pribilincova Z, Baumgartner-Parzer SM, Riedl S, Waldhauser F, Frish H, Stopar-Obreza M, Kržišnik C. Battelino T. Mutational spectrum of steroid 21-hydroxylase and the genotype-phenotype association in the Middle European patients with congenital adrenal hyperplasia. Eur J Endocrinol 2005; 153(1): 99- 106. 26. Witchel SF, Bhamidipati DK, Hoffman EP, Cohen JB. Phenotypic heterogeneity associated with the splicing mutation in congenital adrenal hyperplasia due to 21-hydroxylase deficiency. J Clin Endocrinol Metab 1996; 81(11): 4081- 4088. 27. Speiser PW, Dupont J, Zhu D, Serrat J, Buegeleisen M, Tusie-Luna M-T. Lesser M, New MI, White PC. Disease expression and molecular genotype in congenital adrenal hyperplasia due to 21-hydroxylase deficiency. J Clin Invest 1992; 90(2): 584-595. 28. Higashi Y, Tanae A, Inoue H, Hiromasa T, Fujii-Kuriyama Y. Aberrant splicing and missence mutations cause steroid 21-hydroxylase [P-450(C21)] deficiency in humans: Possible gene conversion products. Proc Natl Acad Sci USA 1988; 85(20): 7486-7490. 29. Day DJ, Speiser PhW, Schulze E, Bettendorf M, Fitness J, Barany F, White PC. Identification of non-amplifying CYP21 genes when using PCR based diagnosis of 21-hydroxylase deficiency in congenital adrenal hyperplasia (CAH) affected pedigrees. Hum Molec Genet 1996; 5(12): 2039- 2048. 30. Dolžan V, Stopar-Obreza M, Žerjav-Tanšek M, Breskvar K, Kržišnik C, Battelino T. 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(2): 137-144. 31. Miller WL. Congenital lipoid adrenal hyperplasia: the human gene knockout for the steroidogenic acute regulatory protein. J Molec Endocrinol 1997; 19(3): 227-240. 32. Rice DA, Kronenberg MS, Mouw AR, Aitken LD, Franklin A, Schimmer BP, Parker KL. Multiple regulatory elements determine adrenocortical expression of steroid 21-hydroxylase. J Biol Chem 1990; 265(14): 8052-8058. 33. Donohoue PA, Collins MM. The human complement C4B/steroid 21-hydroxylase (CYP21) and complement C4A/21-hydroxylase pseudogene (CYP21P) intergenic sequences: comparasion and identification of possible regulatory elements. Biochem Biophys Res Commun 1992; 186(1): 256- 262. 34. Gomes LG, Huang N, Agrawal V, Mendonca BB, Bachega TASS, Miller WL. The common P450 oxidoreductase variant A503V is not a modifier gene for 21-hydroxylase deficiency. J Clin Endocrinol Metab 2008; 93(7): 2913-2916. 35. Wilson RC, Mercado AB, Cheng KC, New MI. Steroid 21-hydroxylase deficiency: Genotype may not predict phenotype. 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