Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Molecular Medicine Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1791-2997 Online ISSN: 1791-3004
Journal Cover
October-2015 Volume 12 Issue 4

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
October-2015 Volume 12 Issue 4

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Case Report Open Access

A duplication upstream of SOX9 was not positively correlated with the SRY‑negative 46,XX testicular disorder of sex development: A case report and literature review

  • Authors:
    • Xin‑Yi Xia
    • Cui Zhang
    • Tian‑Fu Li
    • Qiu‑Yue Wu
    • Na Li
    • Wei‑Wei Li
    • Ying‑Xia Cui
    • Xiao‑Jun Li
    • Yi‑Chao Shi
  • View Affiliations / Copyright

    Affiliations: Department of Reproduction and Genetics, Institute of Laboratory Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu 210002, P.R. China, Department of Reproduction and Genetics, Suzhou Municipal Hospital, Nanjing Medical University Affiliated Suzhou Hospital, Suzhou, Jiangsu 215002, P.R. China
    Copyright: © Xia et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 5659-5664
    |
    Published online on: August 10, 2015
       https://doi.org/10.3892/mmr.2015.4202
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

The 46,XX male disorder of sex development (DSD) is rarely observed in humans. Patients with DSD are all male with testicular tissue differentiation. The mechanism of sex determination and differentiation remains to be elucidated. In the present case report, an 46,XX inv (9) infertile male negative for the sex‑determining region of the Y chromosome (SRY) gene was examined. This infertile male was systemically assessed by semen analysis, serum hormone testing and gonadal biopsy. Formalin‑fixed and paraffin‑embedded gonad tissues were assessed histochemically. The SRY gene was analyzed by fluorescence in situ hybridization (FISH) and polymerase chain reaction (PCR). The other 23 specific loci, including the azoospermia factor region on the Y chromosome and the sequence-targeted sites of the SRY‑box 9 (SOX9) gene were analyzed by PCR. The genes RSPO1, DAX1, SOX3, ROCK, DMRT1, SPRY2 and FGF9 were also assessed using sequencing analysis. Affymetrix Cytogenetics Whole Genome 2.7 M Arrays were used for detecting the genomic DNA from the patient and the parents. The patient with the 46,XX inv (9) (p11q13) karyotype exhibited male primary, however, not secondary sexual characteristics. However, the patient's mother with the 46, XX inv (9) karyotype was unaffected. The testicular tissue dysplasia of the patient was confirmed by tissue biopsy and absence of the SRY gene, and the other 23 loci on the Y chromosome were confirmed by FISH and/or PCR. The RSPO1, DAX1, SOX3, ROCK, DMRT1, SPRY2 and FGF9 genes were sequenced and no mutations were detected. A duplication on the 3 M site in the upstream region of SOX9 was identified in the patient as well as in the mother. The patient with the 46,XX testicular DSD and SRY‑negative status was found to be infertile. The duplication on the 3 M site in the upstream region of SOX9 was a polymorphism, which indicated that the change was not a cause of 46,XX male SDS. These clinical, molecular and cytogenetic findings suggested that other unidentified genetic or environmental factors are significant in the regulation of SDS.
View Figures

Figure 1

Figure 2

Figure 3

View References

1 

Xiao B, Ji X, Xing Y, Chen YW and Tao J: A rare case of 46, XX SRY-negative male with approximately 74-kb duplication in a region upstream of SOX9. Eur J Med Genet. 56:695–698. 2013. View Article : Google Scholar : PubMed/NCBI

2 

Abbas NE, Toublanc JE, Boucekkine C, Toublanc M, Affara NA, Job JC and Fellous M: A possible common origin of 'Y-negative' human XX males and XX true hermaphrodites. Hum Genet. 84:356–360. 1990. View Article : Google Scholar : PubMed/NCBI

3 

Boucekkine C, Toublanc JE, Abbas N, Chaabouni S, Ouahid S, Semrouni M, Jaubert F, Toublanc M, McElreavey K and Vilain E: Clinical and anatomical spectrum in XX sex reversed patients. Relationship to the presence of Y specific DNA-sequences. Clin Endocrinol (Oxf). 40:733–742. 1994. View Article : Google Scholar

4 

McElreavey K, Rappaport R, Vilain E, Abbas N, Richaud F, Lortat-Jacob S, Berger R, Le Coniat M, Boucekkine C and Kucheria K: A minority of 46, XX true hermaphrodites are positive for the Y-DNA sequence including SRY. Hum Genet. 90:121–125. 1992. View Article : Google Scholar : PubMed/NCBI

5 

Ferguson-Smith MA, Cooke A, Affara NA, Boyd E and Tolmie JL: Genotype-phenotype correlations in XX males and their bearing on current theories of sex determination. Hum Genet. 84:198–202. 1990. View Article : Google Scholar : PubMed/NCBI

6 

Ergun-Longmire B, Vinci G, Alonso L, Matthew S, Tansil S, Lin-Su K, McElreavey K and New MI: Clinical, hormonal and cytogenetic evaluation of 46,XX males and review of the literature. J Clin Endocrinol Metab. 18:739–748. 2005.

7 

Vorona E, Zitzmann M, Gromoll J, Schuring AN and Nieschlag E: Clinical, endocrinological, and epigenetic features of the 46,XX male syndrome, compared with 47,XXY Klinefelter patients. J Clin Endocrinol Metab. 92:3458–3465. 2007. View Article : Google Scholar : PubMed/NCBI

8 

Brennan J and Capel B: One tissue, two fates: Molecular genetic events that underlie testis versus ovary development. Nat Rev Genet. 5:509–521. 2004. View Article : Google Scholar : PubMed/NCBI

9 

Meeks JJ, Weiss J and Jameson JL: Dax1 is required for testis determination. Nat Genet. 34:32–33. 2003. View Article : Google Scholar : PubMed/NCBI

10 

Sutton E, Hughes J, White S, Sekido R, Tan J, Arboleda V, Rogers N, Knower K, Rowley L, Eyre H, et al: Identification of SOX3 as an XX male sex reversal gene in mice and humans. J Clin Invest. 121:328–341. 2011. View Article : Google Scholar :

11 

Parma P, Radi O, Vidal V, Chaboissier MC, Dellambra E, Valentini S, Guerra L, Schedl A and Camerino G: R-spondin1 is essential in sex determination, skin differentiation and malignancy. Nat Genet. 38:1304–1309. 2006. View Article : Google Scholar : PubMed/NCBI

12 

Chi L, Itäranta P, Zhang S and Vainio S: Sprouty2 is involved in male sex organogenesis by controlling fibroblast growth factor 9-induced mesonephric cell migration to the developing testis. Endocrinology. 147:3777–3788. 2006. View Article : Google Scholar : PubMed/NCBI

13 

Chiang HS, Wu YN, Wu CC and Hwang JL: Cytogenic and molecular analyses of 46, XX male syndrome with clinical comparison to other groups with testicular azoospermia of genetic origin. J Formos Med Assoc. 112:72–78. 2013. View Article : Google Scholar : PubMed/NCBI

14 

Mizuno K, Kojima Y, Kamisawa H, Moritoki Y, Nishio H, Kohri K and Hayashi Y: Gene expression profile during testicular development in patients with SRY-negative 46,XX testicular disorder of sex development. Urology. 82:1453.e1–e7. 2013. View Article : Google Scholar

15 

Smith CA, McClive PJ, Western PS, Reed KJ and Sinclair AH: Evolution: Conservation of a sex-determining gene. Nature. 402:601–602. 1999. View Article : Google Scholar : PubMed/NCBI

16 

Shan Z, Zabel B, Trautmann U, Hillig U, Ottolenghi C, Wang Y and Haaf T: FISH mapping of the sex-reversal region on human chromosome 9p in two XY females and in primates. Eur J Hum Genet. 8:167–173. 2000. View Article : Google Scholar : PubMed/NCBI

17 

Seeherunvong T, Perera EM, Bao Y, Benke PJ, Benigno A, Donahue RP and Berkovitz GD: 46, XX sex reversal with partial duplication of chromosome arm 22q. Am J Med Genet A. 127:149–151. 2004. View Article : Google Scholar

18 

Huang B, Wang S, Ning Y, Lamb AN and Bartley J: Autosomal XX sex reversal caused by duplication of SOX9. Am J Med Genet. 87:349–353. 1999. View Article : Google Scholar : PubMed/NCBI

19 

Bishop CE, Whitworth DJ, Qin Y, Agoulnik AI, Agoulnik IU, Harrison WR, Behringer RR and Overbeek PA: A transgenic insertion upstream of sox9 is associated with dominant XX sex reversal in the mouse. Nat Genet. 26:490–494. 2000. View Article : Google Scholar : PubMed/NCBI

20 

Vidal VP, Chaboissier MC, de Rooij DG and Schedl A: Sox9 induces testis development in XX transgenic mice. Nat Genet. 28:216–217. 2001. View Article : Google Scholar : PubMed/NCBI

21 

Cox JJ, Willatt L, Homfray T and Woods CG: A SOX9 duplication and familial 46, XX developmental testicular disorder. N Engl J Med. 364:91–93. 2011. View Article : Google Scholar : PubMed/NCBI

22 

Vetro A, Ciccone R, Giorda R, Patricelli MG, Della Mina E, Forlino A and Zuffardi O: XX males SRY negative: A confirmed cause of infertility. J Med Genet. 48:710–712. 2011. View Article : Google Scholar : PubMed/NCBI

23 

Benko S, Gordon CT, Mallet D, Sreenivasan R, Thauvin-Robinet C, Brendehaug A, Thomas S, Bruland O, David M, Nicolino M, et al: Disruption of a long distance regulatory region upstream of SOX9 in isolated disorders of sex development. J Med Genet. 48:825–830. 2011. View Article : Google Scholar : PubMed/NCBI

24 

de la Chapelle A: The etiology of maleness in XX men. Hum Genet. 58:105–116. 1981. View Article : Google Scholar : PubMed/NCBI

25 

Wachtel SS: XX sex reversal in the human Molecular genetics of sex determination. San Diego: Academic; pp. 2071994

26 

Sinclair AH, Berta P, Palmer MS, Hawkins JR, Griffiths BL, Smith MJ, Foster JW, Frischauf AM, Lovell-Badge R and Goodfellow PN: A gene from the human sex-determining region encodes a protein with homology to a conserved DNA-binding motif. Nature. 346:240–244. 1990. View Article : Google Scholar : PubMed/NCBI

27 

Koopman P, Gubbay J, Vivian N, Goodfellow P and Lovell-Badge R: Male development of chromosomally female mice transgenic for Sry. Nature. 351:117–121. 1991. View Article : Google Scholar : PubMed/NCBI

28 

Brennan J and Capel B: One tissue, two fates: Molecular genetic events that underlie testis versus ovary development. Nat Rev Genet. 5:509–521. 2004. View Article : Google Scholar : PubMed/NCBI

29 

Domenice S, Nishi MY, Billerbeck AE, Carvalho FM, Frade EM, Latronico AC, Arnhold IJ and Mendonca BB: Molecular analysis of SRY gene in Brazilian 46,XX sex reversed patients: absence of SRY sequence in gonadal tissue. Med Sci Monit. 7:238–241. 2001.PubMed/NCBI

30 

Ostrer H: Sex determination: Lessons from families and embryos. Clin Genet. 59:207–215. 2001. View Article : Google Scholar : PubMed/NCBI

31 

Sukumaran A, Desmangles JC, Gartner LA and Buchlis J: Duplication of dosage sensitive sex reversal area in a 46, XY patient with normal sex determining region of Y causing complete sex reversal. J Pediatr Endocrinol Metab. 26:775–779. 2013. View Article : Google Scholar : PubMed/NCBI

32 

Qin Y, Kong LK, Poirier C, Truong C, Overbeek PA and Bishop CE: Long-range activation of Sox9 in Odd Sex (Ods) mice. Hum Mol Genet. 13:1213–1218. 2004. View Article : Google Scholar : PubMed/NCBI

33 

Habert R, Lejeune H and Saez JM: Origin, differentiation and regulation of fetal and adult Leydig cells. Mol Cell Endocrinol. 179:47–74. 2001. View Article : Google Scholar : PubMed/NCBI

34 

Gordon CT, Tan TY, Benko S, Fitzpatrick D, Lyonnet S and Farlie PG: Long-range regulation at the SOX9 locus in development and disease. J Med Genet. 46:649–656. 2009. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Xia XY, Zhang C, Li TF, Wu QY, Li N, Li WW, Cui YX, Li XJ and Shi YC: A duplication upstream of SOX9 was not positively correlated with the SRY‑negative 46,XX testicular disorder of sex development: A case report and literature review. Mol Med Rep 12: 5659-5664, 2015.
APA
Xia, X., Zhang, C., Li, T., Wu, Q., Li, N., Li, W. ... Shi, Y. (2015). A duplication upstream of SOX9 was not positively correlated with the SRY‑negative 46,XX testicular disorder of sex development: A case report and literature review. Molecular Medicine Reports, 12, 5659-5664. https://doi.org/10.3892/mmr.2015.4202
MLA
Xia, X., Zhang, C., Li, T., Wu, Q., Li, N., Li, W., Cui, Y., Li, X., Shi, Y."A duplication upstream of SOX9 was not positively correlated with the SRY‑negative 46,XX testicular disorder of sex development: A case report and literature review". Molecular Medicine Reports 12.4 (2015): 5659-5664.
Chicago
Xia, X., Zhang, C., Li, T., Wu, Q., Li, N., Li, W., Cui, Y., Li, X., Shi, Y."A duplication upstream of SOX9 was not positively correlated with the SRY‑negative 46,XX testicular disorder of sex development: A case report and literature review". Molecular Medicine Reports 12, no. 4 (2015): 5659-5664. https://doi.org/10.3892/mmr.2015.4202
Copy and paste a formatted citation
x
Spandidos Publications style
Xia XY, Zhang C, Li TF, Wu QY, Li N, Li WW, Cui YX, Li XJ and Shi YC: A duplication upstream of SOX9 was not positively correlated with the SRY‑negative 46,XX testicular disorder of sex development: A case report and literature review. Mol Med Rep 12: 5659-5664, 2015.
APA
Xia, X., Zhang, C., Li, T., Wu, Q., Li, N., Li, W. ... Shi, Y. (2015). A duplication upstream of SOX9 was not positively correlated with the SRY‑negative 46,XX testicular disorder of sex development: A case report and literature review. Molecular Medicine Reports, 12, 5659-5664. https://doi.org/10.3892/mmr.2015.4202
MLA
Xia, X., Zhang, C., Li, T., Wu, Q., Li, N., Li, W., Cui, Y., Li, X., Shi, Y."A duplication upstream of SOX9 was not positively correlated with the SRY‑negative 46,XX testicular disorder of sex development: A case report and literature review". Molecular Medicine Reports 12.4 (2015): 5659-5664.
Chicago
Xia, X., Zhang, C., Li, T., Wu, Q., Li, N., Li, W., Cui, Y., Li, X., Shi, Y."A duplication upstream of SOX9 was not positively correlated with the SRY‑negative 46,XX testicular disorder of sex development: A case report and literature review". Molecular Medicine Reports 12, no. 4 (2015): 5659-5664. https://doi.org/10.3892/mmr.2015.4202
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team