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A dosage sensitive locus at chromosome Xp21 is involved in male to female sex reversal

Nature Genetics volume 7, pages 497–501 (1994)Cite this article

Abstract

Male to female sex reversal has been observed in individuals with duplications of the short arm of the X chromosome. Here we demonstrate that sex reversal results from the presence of two active copies of an Xp locus rather than from its rearrangement and that alterations at this locus constitute one of the causes of sex reversal in individuals with a normal 46,XY karyotype. We have named this locus DSS (Dosage Sensitive Sex reversal) and localized it to a 160 kilobase region of chromosome Xp21, adjacent to the adrenal hypoplasia congenita locus. The identification of male individuals deleted for DSS suggests that this locus is not required for testis differentiation. We propose that DSS has a role in ovarian development and/or functions as a link between ovary and testis formation.

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References

  1. German, J. et al. Genetically determined sex-reversal in 46,XY humans. Science 202, 53–56 (1978).

    Article  CAS  Google Scholar 

  2. Fechner, P.Y. et al. Report of a kindred with X-linked (or autosomal dominant sex-limited) 46,XY partial gonadal dysgenesis. J. Clin. endocrinol. Methabol. 76, 1248–1252 (1993).

    CAS  Google Scholar 

  3. Bernstein, R. et al. Female phenotype and multiple abnormalities in sibs with a Y chromosome and partial X chromosome duplication: H-Y antigen and Xg blood group findings. J. med. Genet. 17, 291–300 (1980).

    Article  CAS  Google Scholar 

  4. Scherer, G. et al. Duplication of an Xp segment that Includes the ZFX locus causes sex inversion in man. Hum. Genet. 81, 291–294 (1989).

    CAS  PubMed  Google Scholar 

  5. Stern, H.J., Garrity, A.M., Saal, H.M., Wangsa, D. & Disteche, C.M. Duplication Xp21 and sex reversal: Insight into the mechanism of sex determination. Am. J. hum. Genet. 47, suppl, A41 (1990).

    Google Scholar 

  6. May, K.M., Grinzaid, K.A. & Blackston, R.D. Sex reversal and multiple abnormalities due to abnormal segregation of t(X;16)(p11.4;p13.3). Am. J. hum. Genet. 49, suppl, 19 (1991).

    Google Scholar 

  7. Ogata, T. et al. Sex reversal in a child with a 46, X, Yp+ karyotype: support for the existence of a gene(s), located in distal Xp, Involved in testis formation. J. med. Genet. 29, 226–230 (1992).

    Article  CAS  Google Scholar 

  8. Narahara, K., Kodama, Y., Kimura, S. & Kimoto, H. Probable inverted tandem duplication of Xp in a 46,Xp+ boy. Jap. J. hum. Genet. 24, 105–110 (1979).

    Article  CAS  Google Scholar 

  9. Nielsen, K.B. & Langjaer, F. Inherited partial X chromosome duplication in a mentally retarded male. J. med. Genet. 19, 222–236 (1982).

    Article  CAS  Google Scholar 

  10. Bardoni, B. et al. Functional disomy of Xp22-pter in three males carrying a portion of Xp translocated to Yq. Hum. Genet. 91, 333–338 (1993).

    Article  CAS  Google Scholar 

  11. Worley, K.C. et al. Identification of three new markers in Xp21 between DXS28(C7) and DMD. Genomics 13, 957–961 (1992).

    Article  CAS  Google Scholar 

  12. Worley, K.C. et al. Yeast artificial chromosome cloning in the glycerol klnase and adrenal hypoplasia congenita region of Xp21. Genomics 16, 407–416 (1993).

    Article  CAS  Google Scholar 

  13. Walker, A.P. et al. A YAC contig in Xp21 containing the adrenal hypoplasia congenita and glycerol kinase deficiency genes. Hum. molec. Genet. 1, 579–585 (1992).

    Article  CAS  Google Scholar 

  14. McKusick, V.A. in Mendelian Inheritance in Man 10th edn 1841–1843 (Johns Hopkins University Press, Baltimore, 1992).

    Google Scholar 

  15. Berkovitz, G.D. et al. Clinical and pathologic spectrum of 46,XY gonadal dysgenesis: its relevance to the understanding of sex differentiation. Medicine 70, 375–384 (1991).

    Article  CAS  Google Scholar 

  16. Berta, P. et al. Genetic evidence equating SRY and the testis-determining factor. Nature 348, 448–450 (1990).

    Article  CAS  Google Scholar 

  17. Harley, V.R. et al. DNA binding activity of recombinant SRY from normal males and XY females. Science 255, 453–456 (1992).

    Article  CAS  Google Scholar 

  18. Hastie, N.D. Dominant negative mutations In the Wilms tumor (WT1) gene causes Denys-Drash syndrome: proof that a tumor suppressor gene plays a crucial role in normal genitourinary development. Hum. molec. Genet. 1, 293–295 (1992).

    Article  CAS  Google Scholar 

  19. McCabe, E.R.B., Towbin, J.A., van der Engh, G. & Trask, B.J. Xp21 contiguous gene syndromes: deletion quantltation with bivariate flow karyotyping allows mapping of patient breakpoints. Am. J. hum. Genet. 51, 1277–1285 (1992).

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Dutrillaux, B. & Viegas-Pequinot, E. High resolution R-and-G-banding on the same preparation. Hum. Genet. 57, 93–95 (1981).

    Article  CAS  Google Scholar 

  21. Sambrook, J., Fritsch, E.F. & Maniatis, T. in Molecular Cloning: A Laboratory Manual (Cold Spring Harbor Laboratory Press, New York, 1989).

    Google Scholar 

  22. Bardoni, B., Guioli, S., Maserati, E., Maraschio, P. & Camerino, G. A highly conserved sequence on the short arm of chromosome 7 detects multiple polymorphisms. Hum. Genet. 81, 23–25 (1988).

    Article  CAS  Google Scholar 

  23. Franco, B. et al. A gene deleted in Kallmann's syndrome shares homology with neural cell adhesion and axonal path-finding molecules. Nature 353, 529–536 (1991).

    Article  CAS  Google Scholar 

  24. Schaefer, L. et al. A high resolution map of the human Xp22 region. Nature Genet. 4, 272–279 (1993).

    Article  CAS  Google Scholar 

  25. Schlessinger, D., Mandel, J.-L., Monaco, A.P., Nelson, D.L. & Willard, H.F. Report of the fourth international workshop on human X chromosome mapping 1993. Citog. and Cell Genet. 64, 148–194 (1993).

    Google Scholar 

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Author notes

  1. G. Camerino: Correspondence should be addressed to G.C.

Authors and Affiliations

  1. Biologia Generale e Genetica Medica, Universita' di Pavia, via Forlanini 14, 27100, Pavia, Italy

    B. Bardoni, E. Zanaria, S. Guioli, G. Floridia, M. Fraccaro, O. Zuffardi & G. Camerino

  2. Department of Molecular and Human Genetics, Baylor College of Medicine, 1 Baylor Plaza, 77030, Houston, Texas, USA

    K. C. Worley & E. R. B. McCabe

  3. Istituto per l'Infanzia, via dell'Istria 65/1, 34100, Trieste, Italy

    G. Tonini

  4. Istituto di Clinica Pediatrica, Universita' La Sapienza, viale Regina Elena 324, 00161, Roma, Italy

    E. Ferrante

  5. Clinica Pediatrica III, Ospedate S. Raffaele, via Olgettina 60, 20132, Milano, Italy

    G. Chiumello

  6. Istituto di Istologia ed Embriologia, Universita' di Sassari, via S.Pietro 43/B, Sassari, Italy

    G. Camerino

Authors
  1. B. Bardoni
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  2. E. Zanaria
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  3. S. Guioli
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  4. G. Floridia
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  6. G. Tonini
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  7. E. Ferrante
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  8. G. Chiumello
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  9. E. R. B. McCabe
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  10. M. Fraccaro
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  11. O. Zuffardi
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  12. G. Camerino
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Bardoni, B., Zanaria, E., Guioli, S. et al. A dosage sensitive locus at chromosome Xp21 is involved in male to female sex reversal. Nat Genet 7, 497–501 (1994). https://doi.org/10.1038/ng0894-497

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