
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
1. Speiser PW, White PC. Congenital adrenal
hyperplasia. N Engl J Med 2003; 349(8): 776-788.
2. New MI, Lorenzen F, Lerner AJ, Kohn B,
Oberfield SE, Pollack MS, Dupont B, Storner E,
Levy DJ, Pang S, Levine LS. Genotyping steroid
21-hydroxylase deficiency: Hormonal reference
data. J Clin Endocrinol Metab 1983; 57(2): 320-
326.
3. Miller WL, Morel Y. The molecular genetics
of 21-hydroxylase deficiency. Annu Rev Genet
1989; 23:371-393.
4. Speiser PW, New MI, While PC. Molecular
genetic analysis of nonclassic steroid 21-hydroxylase
deficiency associated with HLA-B14,DR1. N Engl
J Med 1988; 319(1): 19-23.
5. Speiser PW, Dupont B, Rubinstein P,
Piazza A, Kastelan A. New MI. High frequency of
nonclassical steroid 21-hydroxylase deficiency. Am
J Hum Genet 1985; 37(4): 650-667.
6. White PC, Speiser PW. Congenital adrenal
hyperplasia due to 21-hydroxylase deficiency.
Endocrinol Rev 2000; 21(3): 245-291.
7. Baumgartner-Parzer SM, Nowotny P, Heinze
G, Waldhäusl W, Vierhapper H. 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. J Clin Endocrinol Metab
1995; 80(8): 2322-2329.
|
|
|
|



 |
Number 27 VOL. 27 (2), 2024 |
Number 27 VOL. 27 (1), 2024 |
Number 26 Number 26 VOL. 26(2), 2023 All in one |
Number 26 VOL. 26(2), 2023 |
Number 26 VOL. 26, 2023 Supplement |
Number 26 VOL. 26(1), 2023 |
Number 25 VOL. 25(2), 2022 |
Number 25 VOL. 25 (1), 2022 |
Number 24 VOL. 24(2), 2021 |
Number 24 VOL. 24(1), 2021 |
Number 23 VOL. 23(2), 2020 |
Number 22 VOL. 22(2), 2019 |
Number 22 VOL. 22(1), 2019 |
Number 22 VOL. 22, 2019 Supplement |
Number 21 VOL. 21(2), 2018 |
Number 21 VOL. 21 (1), 2018 |
Number 21 VOL. 21, 2018 Supplement |
Number 20 VOL. 20 (2), 2017 |
Number 20 VOL. 20 (1), 2017 |
Number 19 VOL. 19 (2), 2016 |
Number 19 VOL. 19 (1), 2016 |
Number 18 VOL. 18 (2), 2015 |
Number 18 VOL. 18 (1), 2015 |
Number 17 VOL. 17 (2), 2014 |
Number 17 VOL. 17 (1), 2014 |
Number 16 VOL. 16 (2), 2013 |
Number 16 VOL. 16 (1), 2013 |
Number 15 VOL. 15 (2), 2012 |
Number 15 VOL. 15, 2012 Supplement |
Number 15 Vol. 15 (1), 2012 |
Number 14 14 - Vol. 14 (2), 2011 |
Number 14 The 9th Balkan Congress of Medical Genetics |
Number 14 14 - Vol. 14 (1), 2011 |
Number 13 Vol. 13 (2), 2010 |
Number 13 Vol.13 (1), 2010 |
Number 12 Vol.12 (2), 2009 |
Number 12 Vol.12 (1), 2009 |
Number 11 Vol.11 (2),2008 |
Number 11 Vol.11 (1),2008 |
Number 10 Vol.10 (2), 2007 |
Number 10 10 (1),2007 |
Number 9 1&2, 2006 |
Number 9 3&4, 2006 |
Number 8 1&2, 2005 |
Number 8 3&4, 2004 |
Number 7 1&2, 2004 |
Number 6 3&4, 2003 |
Number 6 1&2, 2003 |
Number 5 3&4, 2002 |
Number 5 1&2, 2002 |
Number 4 Vol.3 (4), 2000 |
Number 4 Vol.2 (4), 1999 |
Number 4 Vol.1 (4), 1998 |
Number 4 3&4, 2001 |
Number 4 1&2, 2001 |
Number 3 Vol.3 (3), 2000 |
Number 3 Vol.2 (3), 1999 |
Number 3 Vol.1 (3), 1998 |
Number 2 Vol.3(2), 2000 |
Number 2 Vol.1 (2), 1998 |
Number 2 Vol.2 (2), 1999 |
Number 1 Vol.3 (1), 2000 |
Number 1 Vol.2 (1), 1999 |
Number 1 Vol.1 (1), 1998 |
|
|