Non-Syndromic 46,XY Disorders of Sex Development

J Gecz; J Breza; P Banovcin

doi:10.2478/acm-2018-0005

Abstract

Non-syndromic 46,XY DSD (disorders of sex development) represent a phenotypically diversiform group of disorders. We focus on the association between gene variants and the most frequent types of non-syndromic 46,XY DSD, options of molecular genetic testing which has surely taken its place in diagnostics of DSD in the past couple of years. We emphasize the need of molecular genetic testing in individuals with non-syndromic 46,XY DSD in Slovak Republic.

References

1. Hughes IA, Houk C, Ahmed SF, Lee PA. Lawson Wilkins Pediatric Endocrine Society/European Society for Paediatric Endocrinology Consensus G. Consensus statement on management of intersex disorders. J Pediatr Urol. 2006; 2 (3): 148–62.10.1016/j.jpurol.2006.03.004
Search in Google Scholar Back to article
2. Springer A, van den Heijkant M, Baumann S. Worldwide prevalence of hypospadias. J Pediatr Urol. 2016; 12 (3): 152.10.1016/j.jpurol.2015.12.002
Search in Google Scholar Back to article
3. Hutcheson J, Synder HM III. Disorders of Sex Development. 2017. http://emedicine.medscape.com/article/1015520-overview
Search in Google Scholar Back to article
4. Domenice S, Arnhold IJP, Costa EMF et al.. 46,XY Disorders of Sexual Development. [Updated 2017 May 3]. In: De Groot LJ, Chrousos G, Dungan K et al., editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK279170/
Search in Google Scholar Back to article
5. Ahmed SF, Bashamboo A, Lucas-Herald A, McElreavey K. Understanding the genetic aetiology in patients with XY DSD. British Medical Bulletin 2013; 106: 67-89.10.1093/bmb/ldt008
Search in Google Scholar Back to article
6. Aaronson IA. Micropenis: medical and surgical implications. J Urol. 1994 Jul; 152 (1):4-14.10.1016/S0022-5347(17)32804-5
Search in Google Scholar Back to article
7. Kočvara R. Kryptorchizmus. In: Bánovčin P, Buchanec J, Zibolen M. Vybrané kapitoly z nefrológie, Martin, Osveta 2006; 289: 61-69.
Search in Google Scholar Back to article
8. Tošovský VV, Abrahámová J et al.. Kryptorchizmus. Praha, Triton 2004; 180: 52-66.
Search in Google Scholar Back to article
9. Spinoit AF, Claeys T, Bruneel E et al.. Isolated Male Epispadias: Anatomic Functional Restoration Is the Primary Goal. BioMed Research International. 2016; 2016:6983109. doi:10.1155/-2016/6983109.10.1155/2016/6983109
Search in Google Scholar Back to article
10. Gatti JM, Kirsch AJ, Troyer WA et al.. Increased incidence of hypospadias in small-for-gestational age infants in a neonatal intensive-care unit. BJU Int 2001; 87: 548-50.10.1046/j.1464-410X.2001.00088.x
Search in Google Scholar Back to article
11. Ogata T, Wada Y, Fukami M. MAMLD1 (Cxorf6): a new gene for hypospadias. Sex Dev 2008; 2: 244-5.10.1159/00015204018987498
Search in Google Scholar Back to article
12. Thigpen AE, Davis DL, Milatovich A et al.. Molecular genetics of steroid 5 alpha-reductase 2 deficiency. J Clin Invest 1992; 90: 799-809.10.1172/JCI1159543299331522235
Search in Google Scholar Back to article
13. Bouty A, Ayers KL, Pask A et al.. The Genetic and Environmental Factors Underlying Hypospadias. Sexual development: genetics, molecular biology, evolution, endocrinology, embryology, and pathology of sex determination and differentiation 9.5 2015: 239–259. PMC. Web. 26 Mar. 2018.10.1159/000441988501296426613581
Search in Google Scholar Back to article
14. Dong Y, Yi Y, Yao H et al.. Targeted next-Generation Sequencing Identification of Mutations in Patients with Disorders of Sex Development. BMC Medical Genetics 17 2016: 23. PMC. Web. 25 Mar. 2018.10.1186/s12881-016-0286-2479176026980296
Search in Google Scholar Back to article
15. Baxter RM, Arboleda VA, Lee H et al.. Exome Sequencing for the Diagnosis of 46,XY Disorders of Sex Development. J Clin Endocrinol Metab 2015: E333–E344. PMC. Web. 25 Mar. 2018.10.1210/jc.2014-2605431889525383892
Search in Google Scholar Back to article
16. Eggers S et al. “Disorders of Sex Development: Insights from Targeted Gene Sequencing of a Large International Patient Cohort.” Genome Biology 17 (2016): 243. PMC. Web. 25 Mar. 2018.
Search in Google Scholar Back to article
17. Bergman JE, Janssen N, Hoefsloot LH et al.. CHD7 mutations and CHARGE syndrome: the clinical implications of an expanding phenotype. J Med Genet. 2011 May; 48 (5):334–42.10.1136/jmg.2010.08710621378379
Search in Google Scholar Back to article
18. Mohnach L, Fechner PY, Keegan CE. Nonsyndromic Disorders of Testicular Development. 2008 May 21 [Updated 2016 Jun 2]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2018. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1547/.
Search in Google Scholar Back to article
19. Matsumoto AM et Bremner WJ. Defects in Testosterone Biosynthetic Enzymes. In Williams Textbook of Endocrinology (Thirteenth Edition), 2016.
Search in Google Scholar Back to article
20. Pearlman A, Loke J, Le Caignec C et al.. Mutations in MAP3K1 cause 46,XY disorders of sex development and implicate a common signal transduction pathway in human testis determination. Am J Hum Genet. 2010 Dec 10; 87(6): 898–904.10.1016/j.ajhg.2010.11.003299736321129722
Search in Google Scholar Back to article
21. Bashamboo A, Brauner R, Bignon-Topalovic J et al.. Mutations in the FOG2/ZFPM2 gene are associated with anomalies of human testis determination. Hum Mol Genet. 2014 Jul 15; 23 (14): 3657–65.10.1093/hmg/ddu07424549039
Search in Google Scholar Back to article
22. Fukami M, Wada Y, Okada M et al.. Mastermind-like domain-containing 1 (MAMLD1 or Cxorf6) transactivates Hes3 promoter, augments testosterone production, and contains the SF1 target sequence. The Journal of Biological Chemistry. 2008; 283 (9): 525–553210.1074/jbc.M70328920018162467
Search in Google Scholar Back to article
23. Fukami M, Wada Y, Miyabayashi K et al.. CXorf6 is a causative gene for hypospadias. Nature Genetics 2006; 38 (12): 1369-1371.10.1038/ng190017086185
Search in Google Scholar Back to article
24. Kalfa N, Fukami M, Philibert P, et al.. Screening of MAMLD1 Mutations in 70 Children with 46,XY DSD: Identification and Functional Analysis of Two New Mutations. Agoulnik I, ed. PLoS ONE. 2012; 7 (3):e32505. doi:10.1371/journal.pone.0032505.10.1371/journal.pone.0032505331653922479329
Search in Google Scholar Back to article
25. Gottlieb B et Trifiro MA. Androgen Insensitivity Syndrome. 1999 Mar 24 [Updated 2017 May 11]. In: Adam MP, Ardinger HH, Pagon RA et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2018. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1429/
Search in Google Scholar Back to article
26. Okeigwe I et Kuohung W. 5-Alpha reductase deficiency: a 40-year retrospective review. Curr Opin Endocrinol Diabetes Obes 2014; 21 (6): 483-7.10.1097/MED.000000000000011625321150
Search in Google Scholar Back to article
27. Allali S, Muller JB, Brauner R et al.. Mutation analysis of NR5A1 encoding steroidogenic factor 1 in 77 patients with 46,XY disorders of sex development (DSD) including hypospadias. PLoS One. 2011; 6:e24117.10.1371/journal.pone.0024117319757922028768
Search in Google Scholar Back to article
28. Murayama C, Miyazaki H, Miyamoto A et al.. Involvement of Ad4BP/SF-1, DAX-1, and COUP-TFII transcription factor on steroid production and luteinization in ovarian theca cells. Molecular and Cellular Biochemistry 2008; 314 (1-2): 51–58.10.1007/s11010-008-9764-y18409030
Search in Google Scholar Back to article
29. Bertelloni S, Dati E, Baldinotti F et al.. NR5A1 Gene Mutations: Clinical, Endocrine and Genetic Features in Two Girls with 46, XY Disorder of Sex Development. Hormone research in paediatrics. 2014; 81 (2), 104-108.10.1159/000354990
Search in Google Scholar Back to article
30. Wu JY, McGown IN, Lin L et al.. A novel NR5A1 variant in an infant with elevated testosterone from an Australasian cohort of 46,XY patients with disorders of sex development. Clin Endocrinol (Oxf) 2013; 78:545–550.10.1111/cen.12012361375122909003
Search in Google Scholar Back to article
31. Biason-Lauber A. Control of sex development. Best Practice and Research Clinical Endocrinology and Metabolism 2010; 24: 163-186.10.1016/j.beem.2009.12.00220541146
Search in Google Scholar Back to article
32. Tantawy S, Mazen I, Soliman H et al.. Analysis of the gene coding for steroidogenic factor 1 (SF1, NR5A1) in a cohort of 50 Egyptian patients with 46, XY disorders of sex development. European Journal of Endocrinology, 2014; 170 (5), 759–767.10.1530/EJE-13-096524591553
Search in Google Scholar Back to article
33. Baetens D, Stoop H, Peelman F et al.. NR5A1 is a novel disease gene for 46,XX testicular and ovotesticular disorders of sex development. Genet Med 2017; 19(4), 367–376.10.1038/gim.2016.118539259827490115
Search in Google Scholar Back to article
34. Bashamboo A, Ferraz-de-Souza B, Lourenço D et al.. Human male infertility associated with mutations in NR5A1 encoding steroidogenic factor 1. Am J Hum Genet. 2010; 87: 505–512. doi: 10.1016/j.ajhg.2010.09.009.10.1016/j.ajhg.2010.09.009294880520887963
Search in Google Scholar Back to article

Non-Syndromic 46,XY Disorders of Sex Development

Abstract

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