Mutational analysis and genotype-phenotype correlation in patients with classic 21-hydroxylase deficiency from transylvania (North-West Romania)

Journal of Pediatric Endocrinology and Metabolism

Volumn 15, Issue 9, 2002, Pages 1505-1514

  Grigorescu Sido, Anca ^a   Schulze, Egbert ^b   Grigorescu Sido, Paula ^a   Heinrich, Udo ^c   Nistor, Tiberiu ^a   Duncea, Ileana ^a  

^a IULIU HATIEGANU UNIVERSITY OF MEDICINE AND PHARMACY   (Romania)

^b UNIVERSITY OF HEIDELBERG   (Germany)

^c UNIVERSITY HOSPITAL HEIDELBERG   (Germany)

Author keywords

21 Hydroxylase deficiency; Congenital adrenal hyperplasia; Genotype; Mutational analysis; Phenotype; Transylvania

Indexed keywords

DNA; STEROID 21 MONOOXYGENASE;

ADOLESCENT; ADULT; ARTICLE; CHILD; CLINICAL ARTICLE; CONGENITAL ADRENAL HYPERPLASIA; CONTROLLED STUDY; DIAGNOSTIC ACCURACY; DNA DETERMINATION; ETHNIC DIFFERENCE; FEMALE; GENE AMPLIFICATION; GENE CONVERSION; GENE DELETION; GENE MUTATION; GENE SEGREGATION; GENE SEQUENCE; GENOTYPE; GENOTYPE PHENOTYPE CORRELATION; HETEROZYGOSITY; HUMAN; INCIDENCE; LEUKOCYTE; MALE; MUTATIONAL ANALYSIS; PATIENT CARE; POINT MUTATION; POLYMERASE CHAIN REACTION; PRENATAL DIAGNOSIS; ROMANIA; SEQUENCE ANALYSIS; STEROID 21 MONOOXYGENASE DEFICIENCY; TREATMENT OUTCOME;

ADOLESCENT; ADULT; CHILD; CHILD, PRESCHOOL; DNA MUTATIONAL ANALYSIS; FEMALE; GENOTYPE; HUMANS; MALE; MUTATION; PHENOTYPE; ROMANIA; STEROID 21-HYDROXYLASE;

EID: 0036913860     PISSN: 0334018X     EISSN: None     Source Type: Journal    
DOI: 10.1515/JPEM.2002.15.9.1505     Document Type: Article

References (35)

1. New MI, White PC, Pang S, Dupont B, Speiser PW. The adrenal hyperplasia. In: Scriver CR, Beaudet AL, Sly WS, Valle D, eds. The Metabolic Bases of Inherited Disease. New York: McGraw-Hill, 1989; 1881-1918.
2. Krone N, Braun A, Roscher AA, Knorr D, Schwarz HP. Predicting phenotype in 21-hydroxylase deficiency? Comprehensive genotyping in 155 unrelated, well defined patients from Southern Germany. J Clin Endocrinol Metab 2000; 85: 1059-1065.
3. Kominami S, Ochi H, Kobayashi Y, Takemori S. Studies on the steroid hydroxylation system in adrenal cortex microsomes. Purification and characterisation of cytochrome P-450 specific for steroid 21-hydroxylase. J Biol Chem 1980; 255: 3386-3394.
4. New MI, Rapaport R. The adrenal cortex. In: Sperling MA, ed. Pediatric Endocrinology. Philadelphia, PA: WB Saunders Co., 1996; 281-309.
5. New MI. Congenital adrenal hyperplasia. In: de Groot LJ, et al., eds. Endocrinology. Philadelphia, PA: WB Saunders Co., 1995; 1818-1831.
6. Grigorescu-Sido P. Hiperplazia congenitala de corticosuprarenala. In: Grigorescu-Sido P, ed. Tratat elementar de pediatrie, Vol. 2. Cluj: Casa Cartii de Stiinta, 1995; 179-204.
7. Carlson AD, Obeid JS, Canellopoulou N, Wilson RC, New MI. Congenital adrenal hyperplasia: update on prenatal diagnosis and treatment. J Steroid Biochem Mol Biol 1999; 69: 19-29.
8. Speiser PW, Dupont B, Rubinstein P, Piazza A, Kastelan A, New MI. High incidence of nonclassic steroid 21-hydroxylase deficiency. Am J Hum Genet 1985; 37: 650-667.
9. White PC, New MI, Dupont B. Structure of human steroid 21-hydroxylase genes. Proc Natl Acad Sci USA 1986; 83: 5111-5115.
10. Higashi Y, Yoshioka M, 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: 2841-2845.
11. Dupont B, Oberfield SE, Smithwick EM, Lee TD, Levine LS. Close genetic linkage between HLA and congenital adrenal hyperplasia (21-hydroxylase deficiency). Lancet 1977; ii: 1309-1311.
12. Levine LS, Zachmann M, New MI, Prader A, Pollack MS, O'Neil GJ, Yang SY, Oberfield SE, Dupont B. Genetic mapping of the 21-hydroxylase-deficiency gene within the HLA linkage group. N Engl J Med 1978; 299: 911-915.
13. Caroll MC, Campbell RD, Porter RR. Mapping of steroid 21-hydroxylase genes adjacent to complement component C4 genes in HLA, the major histocompatibility complex in man. Proc Natl Acad Sci USA 1985; 82: 521-525.
14. White PC, Vitek A, Dupont B, New MI. Characterisation of frequent deletions causing 21-hydroxylase deficiency. Proc Natl Acad Sci USA 1988; 85: 4436-4440.
15. Higashi Y, Tanae A, Inoue H, Fujii Kuriyama Y. Evidence for frequent gene conversion in the steroid 21-hydroxylase P-450 (C21) gene: implications for steroid 21-hydroxylase deficiency. Am J Hum Genet 1988; 42: 17-25.
16. Wedell A. Molecular genetics of congenital adrenal hypeplasia (21-hydroxylase deficiency): implications for diagnosis, prognosis and treatment. Acta Paediatr 1998; 87: 159-164.
17. Lajic S, Wedell A. An intron 1 splice mutation and a nonsense mutation (W23X) in CYP21 causing severe congenital adrenal hyperplasia. Hum Genet 1996; 98: 182-184.
18. Ezquieta B, Oliver A, Gracia R, Gancedo PG. Analysis of steroid 21-hydroxylase gene mutations in the Spanish population. Hum Genet 1995; 96: 198-204.
19. Wedell A, Thilen A, Ritzen EM, Stengler B, Luthmann H. Mutational spectrum of steroid 21-hydroxylase gene in Sweden: implications for genetic diagnosis and association with disease manifestation. J Clin Endocrinol Metab 1994; 78: 1145-1152.
20. Speiser PW, Dupont J, Zhu D, Serrat J, Beregeleise M, Tsu-Luna MT, Lesse M, New MI, White PC. Disease expression and molecular genotype in congenital adrenal hyperplasia due to 21-hydroxylase deficiency. J Clin Invest 1992; 90: 584-595.
21. Dardis A, Bergada I, Bergada C, Rivarola M, Belgorosky A. Mutation of the steroid 21-hydroxylase gene in an Argentinian population of 36 patients with classical congenital adrenal hyperplasia. J Pediatr Endocrinol Metab 1997; 10: 55-61.
22. Bachega TA, Billerbeck AE, Madureira G, Marcondes JA, Longui CA, Leite AV, Arnhold IJ, Mendonca BB. Molecular genotyping in Brasilian patients with the classical and nonclassical forms of 21-hydroxylase deficiency. J Clin Endocrinol Metab 1998; 83: 4416-4419.
23. Wilson RC, Mercado AB, Cheng KC, New MI. Steroid 21-hydroxylase deficiency: genotype may not predict phenotype. J Clin Endocrinol Metab 1995; 80: 2322-2329.
24. Morel Y, Murena M, Nicolino M, Carel JC, David M, Forest MG. Correlation between genetic lesions of the CYP21B gene and the clinical forms of congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency: report of a large study of 355 CAH chromosomes. Horm Res 1992; 37: 13.
25. Jääskeläinen 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 a well defined population. J Clin Endocrinol Metab 1997; 82: 3293-3297.
26. Ferenczi A, Garami M, Kiss E, Pek M, Sasvari-Szekely M, Barta C, Staub M, Solyom J, Fekete G. Screening for mutations of 21-hydroxylase gene in Hungarian patients with congenital adrenal hyperplasia. J Clin Endocrinol Metab 1999; 84: 2369-2372.
27. Lahiri DK, Nurnberger JI Jr. A rapid non-enzymatic method for preparation of HMW DNA from blood for RFLP studies. Nucleic Acids Res 1991; 19: 5444.
28. Schulze E, Scharer G, Rogatzki A, Priebe L, Lewicka S, Bettendorf M, Hoepffner W, Heinrich UE, Schwabe U. Divergence between genotype and phenotype in relatives of patients with the intron 2 mutation of steroid 21-hydroxylase. Endocr Res 1995; 21: 1359-1364.
29. Beuschlein F, Schulze E, Mora P, Gensheimer HP, Maser-Gluth C, Allolio B, Reincke M. Steroid 21-hydroxylase mutations and 21-hydroxylase messenger ribonucleic acid expression in human adrenocortical tumors. J Clin Endocrinol Metab 1998; 83: 2585-2588.
30. Day DJ, Speiser PW, 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 Mol Gen 1996; 5: 2039-2048.
31. Rumsby G, Avey CJ, Conway GS, Honour JW. Genotype-phenotype analysis in the late onset deficiency in comparison to the classical forms. Clin Endocrinol (Oxf) 1998; 48: 707-711.
32. Balsamo A, Cacciari E, Baldazzi L, Tartaglia L, Cassio A, Mantovani V, Piazzi S, Cicognani A, Pirazzoli P, Mainetti B, Zappula F. CYP21 analysis and phenotype/ genotype relationship in the screened population of the Italian Emilia-Romagna region. Clin Endocrinol (Oxf) 2000; 53: 117-125.
33. Mornet E, Crete P, Kuttenn F, Raux-Demay MC, Boue J, White PC, Boue 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: 79-88.
34. White PC, Speiser PW. Congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Endocr Rev 2000; 21: 245-291.
35. Winkel CA, Casey ML, Worley RJ, Madden JD, MacDonald PC. Extraadrenal steroid 21-hydroxylase activity in a woman with congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency. J Clin Endocrinol Metab 1983; 56: 104-107.