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Mutations in the CYP21B gene in a Chilean population with simple virilizing congenital adrenal hyperplasia

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Abstract

Steroid 21-hydroxylase deficiency (21OHD) compromises about 95% of all cases of congenital adrenal hyperplasia. We have characterized the disease-causing mutations in the steroid 21-hydroxylase genes of 19 Chilean patients (12 females and 7 males) with the simple virilizing (SV) form of 21OHD and compared them with other SV-populations. Using allele-specific polymerase chain reaction, we identified lesions in 28 chromosomes out of 38 tested (73.7%). The most frequent finding was the mutation I173N= 12/38 (31.6%) similar as described in Caucasian, Asian and other Hispanic populations, where this mutation represents around 20–40% of the genetic defects in the CYP21B gene. The mutation V282L=4/38 (10.5%) and deletion (Del) or large gene conversion (LGC)=3/38 (7.9%) were also frequently detected. Only 2 alleles carried the mutation I2 splice (5.3%), this frequency is lower than that reported in Caucasian or in Mexican populations. We did not find alleles with the mutations R357W, Cluster E6, P31L and P454S in these patients. The complete genotype was determined in 11/19 patients (58%) and one allele in 6/19 patients (31.6%). In summary, about 30% of the Chilean population with SV 21OHD presented the missense mutation I173N as described in other populations. The frequency of the other lesions showed differences even between populations with similar genetic background.

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References

  1. New M.I., White P.C., Pang S., Dupont B., Speiser P.W. The adrenal hyperplasias. In: Scriver C.R., Beaudet A.L., Sly W.S., Valle D. (Eds.), The metabolic basis of inherited disease. McGraw-Hill, New York, 1989, vol. 2, pp. 1881–1917.

    Google Scholar 

  2. Pang S., Clark A. Congenital adrenal hyperplasia due to 21-hydroxylase deficiency: newborn screening and its relationship to the diagnosis and treatment of the disorder. Screening 1993, 2: 105–139.

    Article  Google Scholar 

  3. Miller W.L. Genetics, diagnosis and management of 21-hydroxylase deficiency. J. Clin. Endocrinol. Metab. 1994, 78: 241–246.

    CAS  PubMed  Google Scholar 

  4. Higashi Y., Yoshioka H., Yamane M., Gotoh O., Fujii-Kuriyama Y. Complete 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.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  5. White P.C., New M.I., Dupont B. Structure of the human steroid 21-hydroxylase genes. Proc. Natl. Acad. Sci. USA 1986, 83: 5111–5115.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  6. Wedell A. Molecular genetics of congenital adrenal hyperplasia (21-hydroxylase deficiency): implications for diagnosis, prognosis and treatment. Acta Paediatr. 1998, 87: 159–164.

    Article  CAS  PubMed  Google Scholar 

  7. Morel Y., Miller W.L. Clinical and molecular genetics of congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Adv. Hum. Genet. 1991, 133: 368–375.

    Google Scholar 

  8. Fardella C.E., Miller W.L. Molecular biology of mineralocorticoid metabolism. Annu. Rev. Nutr. 1996, 16: 443–470.

    Article  CAS  PubMed  Google Scholar 

  9. New M.I. Diagnosis and management of congenital adrenal hyperplasia. Annu. Rev. Med. 1998, 49: 311–328.

    Article  CAS  PubMed  Google Scholar 

  10. Weddel A. Molecular approaches for the diagnosis of 21-hydroxylase deficiency and congenital adrenal hyperplasia. DNA technology. Clin. Lab. Med. 1996, 16: 125–137.

    Google Scholar 

  11. Fardella C., 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. Clin. Endocrinol. Metab. 1998, 83: 3357–3360.

    CAS  PubMed  Google Scholar 

  12. David M., Forest M.G. Prenatal treatment of congenital adrenal hyperplasia resulting from 21-hydroxylase deficiency. J. Pediatr. 1984, 105: 779–803.

    Article  Google Scholar 

  13. Speiser P.W., Laforgia N., Kato K., Pareira J., Khan R., Yang S.Y., Whorwood C., White P.C., Elias S., Schriock ??, Simpson J.L., Taslimi M., Najjar J., May S., Mills G., Crawford C., New M. First trimester prenatal treatment and molecular genetic diagnosis of congenital adrenal hyperplasia (21-hydroxylase deficiency). [Review]. J. Clin. Endocrinol. Metab. 1990, 70: 838–848.

    Article  CAS  PubMed  Google Scholar 

  14. Forest M.G., David M., Morel Y. Prenatal diagnosis and treatment of 21-hydroxylase deficiency. J. Steroid Biochem. Mol. Biol. 1993, 45: 75–82.

    Article  CAS  PubMed  Google Scholar 

  15. Lahiri D., Nurnberger J. A rapid non-enzimatic method for the preparation of HMW DNA from blood for RFLP studies. Nucleic. Acids Res. 1991, 19: 5444.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  16. Weddel A., Luthman H. Steroid 21-hydroxylase deficiency: two additional mutations in salt-wasting disease and rapid screening of disease-causing mutations. Hum. Mol. Genet. 1993, 2: 499–504.

    Article  Google Scholar 

  17. Wedell A., Thilén A., Ritzén M., Stengler B., Luthman H. 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.

    CAS  PubMed  Google Scholar 

  18. Wilson R., Wei J.Q., Cheng K.C., Mercado M., New M. 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.

    CAS  PubMed  Google Scholar 

  19. Speiser P.W., Dupont J., Zhu D., Serrat J., Buegeleisen M., Tusie-Luna M.T., Lesser M., New M.I., White P.C. Disease expression and molecular genotype in congenital adrenal hyperplasia due to 21-hydroxylase deficiency. J. Clin. Invest. 1992, 90: 584–595.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  20. Carrera P., Bordone L., Azzani T., Brunelli V., Garancini M.P., Chiumello G., Ferrari M. Point mutations in Italian patients with classic, non-classic, and cryptic forms of steroid 21-hydroxylase deficiency. Hum. Genet. 1996, 98: 662–665.

    Article  CAS  PubMed  Google Scholar 

  21. Carrera P., Ferrari M., Beccaro F., Spiga I., Zanussi M., Rigon F., Braggion F., Zacchello F., Greggio N. Molecular characterization of 21-hydroxylase deficiency in 70 Italian families. Hum. Hered. 1993, 43: 190–196.

    Article  CAS  PubMed  Google Scholar 

  22. Barbat B., Bogyo A., Raux-Demay M.C., Kuttenn F., Boué J., Simon-Bouy B., Serre J.L., Boué A., Mornet E. Screening of CYP21 gene mutations in 129 French patients affected by steroid 21hydroxylase deficiency. Hum. Mutat. 1995, 5: 126–130.

    Article  CAS  PubMed  Google Scholar 

  23. Higashi Y., Hiromasa T., Tanae A., Miki T., Nakura Y., Kondo T., Ohura T., Ogawa E., Nakayama K., Fujii-Kuriyama Y. Effects of individual mutations in the P-450(c21) activity and their distribution in the patients genomes of congenital steroid 21-hydroxylase deficiency. J. Biochem. 1991, 109: 638–644.

    CAS  PubMed  Google Scholar 

  24. Dardis A., Bergada I., Rivarola M., Belgorosky A. Mutations 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.

    Article  CAS  PubMed  Google Scholar 

  25. Ordoñez-Sanchez M.L., Ramirez-Jimenez S., Lopez-Gutierrez A.U., Riba L., Gamboa-Cardiel S., Cerrillo-Hinojosa M., Altamirano-Bustamante N., Calzada-León R., Robles-Valdez C., Mendoza-Morfin F., Tusie-Luna T. Molecular genetic analysis of patients carring 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.

    Article  PubMed  Google Scholar 

  26. Cruz-Coke R., Moreno R.S. Genetic epidemiology of single gene defects in Chile. J. Med. Genet. 1994, 31: 702–706.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  27. Lisker R., Ramirez E., Briceno R.P., Granados J., Babinsky V. Gene frequencies and admixture estimates in four Mexican urban centers. Hum. Biol. 1990, 62: 791–801.

    CAS  PubMed  Google Scholar 

  28. Tiburcio V., Romero A., De Garay A.L. Gene frequencies and racial intermixture in a mestizo population from Mexico City. Ann. Hum. Biol. 1978, 5: 131–138.

    Article  CAS  PubMed  Google Scholar 

  29. Wallace D.C., Torroni A. American indian prehistory as written in the mitochondrial DNA: a review. Hum. Biol. 1992, 64: 403–416.

    CAS  PubMed  Google Scholar 

  30. Tusié-Luna M.T., Ramírez-Jiménez S., Ordóñez-Sánchez M.L., Cabello-Villegas J., Altamirano-Bustamante N., Calzada-León R., Robles-Valdés C., Mendoza-Morfín F., Méndez J.P., Terán-García ??. Low frequency of deletion alleles in patients with steroid 21-hydroxylase deficiency in a Mexican population. Hum. Genet. 1996, 98: 376–379.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Endocrinology, P. Universidad Catolica de Chile, Lira 44, Santiago, Chile

    Carlos E. Fardella & A. Cattani

  2. Research and Development Unit of the Clinical Laboratory Service, Faculty of Medicine, Catholic University of Chile, Chile

    H. Poggi, J. Soto & A. Foradori

  3. Endocrinology Service, Sotero del Rio and Luis Calvo Mackenna Hospitals, Public Health Services, Chile

    I. Torrealba

  4. Department of Endocrinology, Exequiel Gonzalez Cortez Hospital, Chile

    F. Ugarte

  5. Department of Endocrinology, San Borja Arriaran Hospital, Santiago, Chile

    A. Cortinez

Authors
  1. Carlos E. Fardella
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  2. H. Poggi
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  3. J. Soto
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  4. I. Torrealba
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  5. A. Cattani
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  6. F. Ugarte
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  7. A. Cortinez
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  8. A. Foradori
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Fardella, C.E., Poggi, H., Soto, J. et al. Mutations in the CYP21B gene in a Chilean population with simple virilizing congenital adrenal hyperplasia. J Endocrinol Invest 23, 412–416 (2000). https://doi.org/10.1007/BF03343746

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