Volume 17, Issue 6 (June 2019 2019)                   IJRM 2019, 17(6): 451-456 | Back to browse issues page

XML Persian Abstract Print

Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:
Nazari M, Mehrjardi M Y V, Neghab N, Aghabagheri M, Ghasemi N. A novel mutation in CYP17A1 gene leads to congenital adrenal hyperplasia: A case report. IJRM 2019; 17 (6) :451-456
URL: http://ijrm.ir/article-1-1563-en.html
A novel mutation in CYP17A1 gene leads to congenital adrenal hyperplasia: A case report
Majid Nazari1 , Mohammad Yahya Vahidi Mehrjardi2 , Nosrat Neghab3 , Mahdi Aghabagheri4 , Nasrin Ghasemi * 5
1- Department of Medical Genetics, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
2- Medical Genetics Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
3- Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
4- Meybod Nursing School, Yazd, Iran.
5- Abortion Research Centre, Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
Abstract:   (2002 Views)
Background: Congenital adrenal hyperplasia is a rare autosomal recessive disorder where the mutation in P450 family 17 subfamily A member 1 gene (CYP17A1) is involved in its etiology. The disorder represents itself with low blood levels of estrogens, androgens, and cortisol that generally couples with hypertension, Hypokalemia, sexual primary amenorrhea, infantilism and in affected individuals.
Case: In this study, the CYP17A1 gene in a 14-year-old female was examined. The karyotype of the patient was 46, XX, and the analysis of the CYP17A1 gene by Sanger sequencing revealed a novel homozygous deletion c.1052-1054CCT which led to isolated 17,20-lyase deficiency.
Conclusion: In conclusion, this study report an in-frame deletion which results in isolated 17, 20-lyase deficiency, and the mutation might be used for diagnosis in other patients with distinctive clinical symptoms.
Keywords: Congenital adrenal hyperplasia (CAH), CYP17A1 gene, Ambiguous genitalia.
Full-Text [PDF 442 kb]   (664 Downloads) |   |   Full-Text (HTML)  (442 Views)  
Type of Study: Case Report |
References
1. Merke DP, Bornstein SR, Avila NA, Chrousos GP. NIH conference. Future directions in the study and management of congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Ann Intern Med 2002; 136: 320-334. [DOI:10.7326/0003-4819-136-4-200202190-00012] [PMID]
2. DeVore NM, Scott EE. Structures of cytochrome P450 17A1 with prostate cancer drugs abiraterone and TOK-001. Nature 2012; 482: 116-119. [DOI:10.1038/nature10743] [PMID] [PMCID]
3. Matteson KJ, Picado-Leonard J, Chung BC, Mohandas TK, Miller WL. Assignment of the gene for adrenal p450cl7 (steroid 17α-hydr0xylase⁄ 17, 20 lyase) to human chromosome 10. J Clin Endocrinol Metab 1986; 63: 789-791. [DOI:10.1210/jcem-63-3-789] [PMID]
4. Picado-Leonard J, Miller WL. Cloning and sequence of the human gene for P450cl7 (steroid 17α-hydroxylase/17, 20 lyase): similarity with the gene for P450c21. DNA 1987; 6: 439-448. [DOI:10.1089/dna.1987.6.439] [PMID]
5. Chung BC, Picado-Leonard J, Haniu M, Bienkowski M, Hall PF, Shively JE, et al. Cytochrome P450c17 (steroid 17 alpha-hydroxylase/17, 20 lyase): cloning of human adrenal and testis cDNAs indicates the same gene is expressed in both tissues. Proc Nati Acad Sci USA 1987; 84: 407-411. [DOI:10.1073/pnas.84.2.407] [PMID] [PMCID]
6. Miller WL, Auchus RJ. The molecular biology, biochemistry, and physiology of human steroidogenesis and its disorders. Endocr Rev 2011; 32: 81-151. [DOI:10.1210/er.2010-0013] [PMID] [PMCID]
7. Yanase T, Simpson ER, Waterman MR. 17α-hydroxylase/17, 20-lyase deficiency: from clinical investigation to molecular definition. Endocr Rev 1991; 12: 91-108. [DOI:10.1210/edrv-12-1-91] [PMID]
8. Krone N, Dhir V, Ivison HE, Arlt W. Congenital adrenal hyperplasia and P450 oxidoreductase deficiency. Clin Endocrinol 2007; 66: 162-172. [DOI:10.1111/j.1365-2265.2006.02740.x] [PMID]
9. Auchus RJ. The genetics, pathophysiologx, and management of human deficiencies of P450c17. Endocrinol Metab Clin North Am 2001; 30: 101-119. [DOI:10.1016/S0889-8529(08)70021-5]
10. Biason-Lauber A, Leiberman E, Zachmann M. A single amino acid substitution in the putative redox partner-binding site of P450c17 as cause of isolated 17, 20-lyase deficiency. J Clin Endocrinol Metab 1997; 82: 3807-3812. [DOI:10.1210/jc.82.11.3807]
11. Sherbet DP, Tiosano D, Kwist KM, Hochberg Z, Auchus RJ. CYP17 mutation E305G causes isolated 17, 20-lyase deficiency by selectively altering substrate binding. J Biol Chem 2003; 278: 48563-48569. [DOI:10.1074/jbc.M307586200] [PMID]
12. Turkkahraman D, Guran T, Ivison H, Griffin A, Vijzelaar R, Krone N. Identification of a novel large CYP17A1 deletion by MLPA analysis in a family with classic 17α-hydroxylase deficiency. Sex Dev 2015; 9: 91-97. [DOI:10.1159/000375183] [PMID]
13. Brooke AM, Taylor NF, Shepherd JH, Gore ME, Ahmad T, Lin L, et al. A novel point mutation in P450c17 (CYP17) causing combined 17α-hydroxylase/17, 20-lyase deficiency. J Clin Endocrinol Metab 2006; 91: 2428-2431. [DOI:10.1210/jc.2005-2653] [PMID]
14. van Den Akker EL, Koper JW, Boehmer AL, Themmen AP, Verhoef-Post M, Timmerman MA, et al. Differential inhibition of 17α-hydroxylase and 17, 20-lyase activities by three novel missense CYP17 mutations identified in patients with P450c17 deficiency. J Clin Endocrinol Metabo 2002; 87: 5714-5721. [DOI:10.1210/jc.2001-011880] [PMID]
15. Oh YK, Ryoo U, Kim D, Cho SY, Jin DK, Yoon BK, et al. 17α-hydroxlyase/17, 20-lyase deficiency in three siblings with primary amenorrhea and absence of secondary sexual development. J Pediatr Adolesc Gynecol 2012; 25: e103-e105. [DOI:10.1016/j.jpag.2012.05.008] [PMID]
16. Biglieri EG, Herron MA, Brust N. 17-hydroxylation deficiency in man. J Clin Invest 1966; 45: 1946-1954. [DOI:10.1172/JCI105499] [PMID] [PMCID]
17. Speroff L, Fritz MA. Clinical gynecologic endocrinology and infertility. 8th ed. Philadelphia: Lipppincott Williams & Wilkins; 2011.
18. Attard G, Reid AH, Auchus RJ, Hughes BA, Cassidy AM, Thompson E, et al. Clinical and biochemical consequences of CYP17A1 inhibition with abiraterone given with and without exogenous glucocorticoids in castrate men with advanced prostate cancer. J Clin Endocrinol Metab 2012; 97: 507-516. [DOI:10.1210/jc.2011-2189] [PMID]
19. Geller DH, Auchus RJ, Mendonça BB, Miller WL. The genetic and functional basis of isolated 17, 20-lyase deficiency. Nat Genet 1997; 17: 201-205. [DOI:10.1038/ng1097-201] [PMID]
20. Hershkovitz E, Parvari R, Wudy SA, Hartmann MF, Gomes LG, Loewental N, et al. Homozygous mutation G539R in the gene for P450 oxidoreductase in a family previously diagnosed as having 17, 20-lyase deficiency. J Clin Endocrinol Metab 2008; 93: 3584-3588. [DOI:10.1210/jc.2008-0051] [PMID] [PMCID]
21. Kok RC, Timmerman MA, Wolffenbuttel KP, Drop SL, de Jong FH. Isolated 17, 20-lyase deficiency due to the cytochrome b5 mutation W27X. J Clin Endocrinol Metab 2010; 95: 994-999. [DOI:10.1210/jc.2008-1745] [PMID]
Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

Designed & Developed by : Yektaweb