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Year 2018, Volume: 35 Issue: 3, 63 - 69, 31.10.2019

Abstract

References

  • Concolino, P., et al. (2009). "Multiplex ligation-dependent probe amplification (MLPA) assay for the detection of CYP21A2 gene deletions/duplications in congenital adrenal hyperplasia: first technical report." Clinica chimica acta 402(1-2): 164-170.
  • Delague, V., et al. (2000). "Mutational analysis in Lebanese patients with congenital adrenal hyperplasia due to a deficit in 21-hydroxylase." Hormone Research in Paediatrics 53(2): 77-82.
  • Dolž, V., et al. (2005). "Mutational spectrum of steroid 21-hydroxylase and the genotype-phenotype association in Middle European patients with congenital adrenal hyperplasia." European Journal of Endocrinology 153(1): 99-106.
  • Eugster, E. A. and O. H. Pescovitz (2002). Developmental Endocrinology: From Research to Clinical Practice, Springer Science & Business Media.
  • Forsham, P. H. and F. S. Greenspan (1983). Basic & clinical endocrinology, Lange medical publications.
  • Gonçalves, J., et al. (2007). "Congenital adrenal hyperplasia: focus on the molecular basis of 21-hydroxylase deficiency." Expert reviews in molecular medicine 9(11): 1-23.
  • Goossens, K., et al. (2009). "Lack of correlation between phenotype and genotype in untreated 21‐hydroxylase‐deficient Indonesian patients." Clinical endocrinology 71(5): 628-635.
  • Kelestimur, F., et al. (2009). "The frequency of CYP 21 gene mutations in Turkish women with hyperandrogenism." Experimental and clinical endocrinology & diabetes 117(05): 205-208.
  • Kharrat, M., et al. (2004). "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." The Journal of Clinical Endocrinology & Metabolism 89(1): 368-374.
  • New, M. I. and Z. Rosenwaks (2019). "Introduction: Contemporary perspectives on congenital adrenal hyperplasia: impacts on reproduction." Fertility and sterility 111(1): 4-6.
  • Ohlsson, G., et al. (1999). "Steroid 21‐hydroxylase deficiency: Mutational spectrum in Denmark, three novel mutations, and in vitro expression analysis." Human mutation 13(6): 482-486.
  • Rimoin, D. L., et al. (2007). Emery and Rimoin's principles and practice of medical genetics, Churchill Livingstone Elsevier.
  • Rooney, D. E. and B. Czepulkowski (2001). Human cytogenetics: constitutional analysis: a practical approach, Oxford University Press, USA.
  • Sadeghi, F., et al. (2008). "Identification of frequency and distribution of the nine most frequent mutations among patients with 21-hydroxylase deficiency in Turkey." Journal of Pediatric Endocrinology and Metabolism 21(8): 781-788.
  • Torresani, T. and A. Biason‐Lauber (2007). "Congenital adrenal hyperplasia: diagnostic advances." Journal of Inherited Metabolic Disease: Official Journal of the Society for the Study of Inborn Errors of Metabolism 30(4): 563-575.
  • White, P. C. and P. W. Speiser (2000). "Congenital adrenal hyperplasia due to 21-hydroxylase deficiency." Endocrine reviews 21(3): 245-291.
  • Wilson, R., et al. (1995). "Steroid 21-hydroxylase deficiency: genotype may not predict phenotype." The Journal of Clinical Endocrinology & Metabolism 80(8): 2322-2329.

Correlation of phenotype with the CYP21 gene mutation analysis of classic type congenital adrenal hyperplasia due to 21-Hydroxylase deficiency

Year 2018, Volume: 35 Issue: 3, 63 - 69, 31.10.2019

Abstract

INTRODUCTION

Ambiguous genitalia is seen as the most
common phenotypic reflection of sexual development disorders. Congenital
adrenal hyperplasia (CAH) is the most common cause of ambiguous genitalia,
while the most common cause of CAH is a 21-hydroxylase deficiency with a rate
of 90-95%. The disease is caused by mutations in the CYP21A2 gene located at
6p21.3. It is inherited in an autosomal recessive manner. Seven previously
identified point mutations,  an 8-bp
deletion and large deletions, have significant role in the etiology of the
disease.

In this study, we aimed to report CYP21
molecular genetic evaluation by RFLP and MLPA methods in classic CAH patients
with 21-hydroxylase deficiency.

MATERIAL
AND METHODS

In this study, 26 patients with pre-diagnosis
of Classic Type Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency
were reported. Seven previously identified point mutations, an 8-bp deletion,
and large deletions were analyzed by PCR-RFLP methods in the patient group.

For the MLPA study, SALSA MLPA KIT P050-B2
CAH (Lot0408) kit which was produced by MRC Holland was used.

RESULTS

In 21 (80%) of 26 patients analyzed, causative
mutations were found. The most frequent mutation was the large deletions (6
patients, 12 allels), accounting 23% of the patients.

CONCLUSION

















In 21 (80.7%) of 26 patients, the causative
mutations were found by using PCR (8-bp del. and large deletions) and RFLP (7
known point mutations) methods. MLPA
analysis confirmed all of the deletions detected by PCR-RFLP, and the 83% of
the detectable point mutations with MLPA. A complete genotype-phenotype
relationship could be established in all patients in whom mutation could be
detected in the study group.

References

  • Concolino, P., et al. (2009). "Multiplex ligation-dependent probe amplification (MLPA) assay for the detection of CYP21A2 gene deletions/duplications in congenital adrenal hyperplasia: first technical report." Clinica chimica acta 402(1-2): 164-170.
  • Delague, V., et al. (2000). "Mutational analysis in Lebanese patients with congenital adrenal hyperplasia due to a deficit in 21-hydroxylase." Hormone Research in Paediatrics 53(2): 77-82.
  • Dolž, V., et al. (2005). "Mutational spectrum of steroid 21-hydroxylase and the genotype-phenotype association in Middle European patients with congenital adrenal hyperplasia." European Journal of Endocrinology 153(1): 99-106.
  • Eugster, E. A. and O. H. Pescovitz (2002). Developmental Endocrinology: From Research to Clinical Practice, Springer Science & Business Media.
  • Forsham, P. H. and F. S. Greenspan (1983). Basic & clinical endocrinology, Lange medical publications.
  • Gonçalves, J., et al. (2007). "Congenital adrenal hyperplasia: focus on the molecular basis of 21-hydroxylase deficiency." Expert reviews in molecular medicine 9(11): 1-23.
  • Goossens, K., et al. (2009). "Lack of correlation between phenotype and genotype in untreated 21‐hydroxylase‐deficient Indonesian patients." Clinical endocrinology 71(5): 628-635.
  • Kelestimur, F., et al. (2009). "The frequency of CYP 21 gene mutations in Turkish women with hyperandrogenism." Experimental and clinical endocrinology & diabetes 117(05): 205-208.
  • Kharrat, M., et al. (2004). "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." The Journal of Clinical Endocrinology & Metabolism 89(1): 368-374.
  • New, M. I. and Z. Rosenwaks (2019). "Introduction: Contemporary perspectives on congenital adrenal hyperplasia: impacts on reproduction." Fertility and sterility 111(1): 4-6.
  • Ohlsson, G., et al. (1999). "Steroid 21‐hydroxylase deficiency: Mutational spectrum in Denmark, three novel mutations, and in vitro expression analysis." Human mutation 13(6): 482-486.
  • Rimoin, D. L., et al. (2007). Emery and Rimoin's principles and practice of medical genetics, Churchill Livingstone Elsevier.
  • Rooney, D. E. and B. Czepulkowski (2001). Human cytogenetics: constitutional analysis: a practical approach, Oxford University Press, USA.
  • Sadeghi, F., et al. (2008). "Identification of frequency and distribution of the nine most frequent mutations among patients with 21-hydroxylase deficiency in Turkey." Journal of Pediatric Endocrinology and Metabolism 21(8): 781-788.
  • Torresani, T. and A. Biason‐Lauber (2007). "Congenital adrenal hyperplasia: diagnostic advances." Journal of Inherited Metabolic Disease: Official Journal of the Society for the Study of Inborn Errors of Metabolism 30(4): 563-575.
  • White, P. C. and P. W. Speiser (2000). "Congenital adrenal hyperplasia due to 21-hydroxylase deficiency." Endocrine reviews 21(3): 245-291.
  • Wilson, R., et al. (1995). "Steroid 21-hydroxylase deficiency: genotype may not predict phenotype." The Journal of Clinical Endocrinology & Metabolism 80(8): 2322-2329.
There are 17 citations in total.

Details

Primary Language English
Subjects Health Care Administration
Journal Section Clinical Research
Authors

Berk Özyılmaz 0000-0003-2654-3698

Murat Aydın

Gönül Oğur

Publication Date October 31, 2019
Submission Date March 31, 2019
Acceptance Date August 26, 2019
Published in Issue Year 2018 Volume: 35 Issue: 3

Cite

APA Özyılmaz, B., Aydın, M., & Oğur, G. (2019). Correlation of phenotype with the CYP21 gene mutation analysis of classic type congenital adrenal hyperplasia due to 21-Hydroxylase deficiency. Journal of Experimental and Clinical Medicine, 35(3), 63-69.
AMA Özyılmaz B, Aydın M, Oğur G. Correlation of phenotype with the CYP21 gene mutation analysis of classic type congenital adrenal hyperplasia due to 21-Hydroxylase deficiency. J. Exp. Clin. Med. October 2019;35(3):63-69.
Chicago Özyılmaz, Berk, Murat Aydın, and Gönül Oğur. “Correlation of Phenotype With the CYP21 Gene Mutation Analysis of Classic Type Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency”. Journal of Experimental and Clinical Medicine 35, no. 3 (October 2019): 63-69.
EndNote Özyılmaz B, Aydın M, Oğur G (October 1, 2019) Correlation of phenotype with the CYP21 gene mutation analysis of classic type congenital adrenal hyperplasia due to 21-Hydroxylase deficiency. Journal of Experimental and Clinical Medicine 35 3 63–69.
IEEE B. Özyılmaz, M. Aydın, and G. Oğur, “Correlation of phenotype with the CYP21 gene mutation analysis of classic type congenital adrenal hyperplasia due to 21-Hydroxylase deficiency”, J. Exp. Clin. Med., vol. 35, no. 3, pp. 63–69, 2019.
ISNAD Özyılmaz, Berk et al. “Correlation of Phenotype With the CYP21 Gene Mutation Analysis of Classic Type Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency”. Journal of Experimental and Clinical Medicine 35/3 (October 2019), 63-69.
JAMA Özyılmaz B, Aydın M, Oğur G. Correlation of phenotype with the CYP21 gene mutation analysis of classic type congenital adrenal hyperplasia due to 21-Hydroxylase deficiency. J. Exp. Clin. Med. 2019;35:63–69.
MLA Özyılmaz, Berk et al. “Correlation of Phenotype With the CYP21 Gene Mutation Analysis of Classic Type Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency”. Journal of Experimental and Clinical Medicine, vol. 35, no. 3, 2019, pp. 63-69.
Vancouver Özyılmaz B, Aydın M, Oğur G. Correlation of phenotype with the CYP21 gene mutation analysis of classic type congenital adrenal hyperplasia due to 21-Hydroxylase deficiency. J. Exp. Clin. Med. 2019;35(3):63-9.