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Génétique moléculaire des dysgénésies testiculaires

Molecular genetic of testis dysgenesis

Andrologie volume 4, pages 30–36 (1994)Cite this article

Resume

La détermination testiculaire, première étape de la différenciation sexuelle masculine, est sous le contrôle de facteurs génétiques. Le rôle clé du gène SRY dans ces mécanismes est maintenant bien établi. Cependant de nombreux arguments, cliniques et génétiques, plaident en faveur de l’intervention d’autres gènes en aval ou en amont de SRY.

Ainsi, la plupart des hommes 46, XX ont hérité, par translocation, du gène SRY, responsable de la différenciation des gonades dans le sens testiculaire, mais dans 10% des cas le gène SRY n’est pas retrouvé. De même, si l’analyse de femmes 46, XY a participé à l’identification du gène SRY, 80% des cas de dysgénésies gonadiques ne sont pas expliqués par une anomalie de SRY.

Un certain nombre de situations cliniques permettent de suspecter le rôle des autosomes (chromosomes 1, 9, 10 17 …) et du chromosome X dans la pathologie de la détermination sexuelle. Les travaux les plus avancés concernent le facteur TDF-X, qui agirait comme un represseur de la détermination testiculaire.

Au total, les mécanismes moléculaires de la détermination sexuelle apparaissent extrêmement complexes, faisant intervenir probablement plusieurs gènes en une cascades de réactions.

Abstract

The first step of male differentiation is the testis determination which is genetically controled. The key role of SRY gene is now established. However, a number of clinical and genetic data favoured the role of other genes taking place upstream or downstream SRY.

Most of 46, XX males possess a translocated SRY gene and thus develop testis, but SRY gene is not found in 10% of such patients. Likewise, the molecular study of 46, XY females participated in the identification of SRY as testis determining factor, but 80% of XY gonadal dysgenesis are not explained by an abnormality of SRY gene.

Several clinical situations permitted to suspect the role of autosomal (chromosome 1, 9, 10 17 …) and X chromosome loci in the pathology of sex determination. Some recent works concern, in particular, the testis determining factor of the X chromosome (TDF-X) that could act as a repressor of the testis differentiation.

In conclusion, molecular mechanisms of sexual determination appear to be much complex, involving probably several genes in a pathway that remain to be elucidated.

References

  1. BENNETT CP, DOCHERTY Z, ROBB SA, ET AL.: Deletion of 9p and sex reversal. J. Med. Genet, 1993, 30: 518–520.

    Article  PubMed  CAS  Google Scholar 

  2. BERTA P, HAWKINS JR, SINCLAIR AH, ET AL.: Genetic evidence equating SRY and the testis-determining factor. Nature, 1990, 348: 448–450.

    Article  PubMed  CAS  Google Scholar 

  3. BERTA P, MORIN D, POULAT F, ET AL.: Molecular analysis of the sex determining region from the Y chromosome in two patients with Frasier syndrome. Horm. Res, 1992, 37: 103–106.

    Article  PubMed  CAS  Google Scholar 

  4. HAWKINS JR, TAYLOR A, BERTA P, ET AL.: Mutational analysis of SRY: nonsense and missense mutations in XY sex reversal. Hum. Genet, 1992, 88: 471–474.

    Article  PubMed  CAS  Google Scholar 

  5. HUFF DS, WU HY, SNYDER MMI, ET AL.: Evidence in favor of the mechanical (intrauterine torsion) theory over the endocrinopathy (cryptorchidism) theory in the pathogenesis of testicular agenesis. J. Urol, 1991, 146: 630–631.

    PubMed  CAS  Google Scholar 

  6. JÄGER RJ, ANVRET M, HALL K AND SCHERER G.: A human XY female with a frame shift mutation in the candidate testis-determining gene SRY. Nature, 1990, 348: 452–453.

    Article  PubMed  Google Scholar 

  7. JÄGER RJ, HARLEY VR, PFEIFFER RA, GOODFELLOW PN AND SCHERER G.: A familial mutation in the Testis-Determining gene SRY shared by both sexes. Hum. Genet, 1992, 90: 350–355.

    Article  PubMed  Google Scholar 

  8. LOBACCARO JM, MEDLEJ R, BERTA P, ET AL.: PCR analysis and sequencing of the SRY sex determining gene in patients with bilateral congenital anorchia. Clin. Endocrinol, 1993, 38: 197–201.

    Article  CAS  Google Scholar 

  9. LOBACCARO JM AND SULTAN C.: La différenciation sexuelle normale: génétique et endocrinologie moléculaire. C. R. Soc. Biol, 1992, 186: 314–331.

    CAS  Google Scholar 

  10. MCELREAVEY K, VILAIN E, BOUCEKKINE C, ET AL.: XY sex reversal associated with a nonsense mutation in SRY. Genomics, 1992, 13: 838–840.

    Article  PubMed  CAS  Google Scholar 

  11. MCELREAVY K, VILAIN E, ABBAS N, ET AL.: XY sex reversal associated with a deletion 5′ to the SRY HMG box in the Testis-Determining region. Proc Natl Acad Sci USA, 1992, 89: 11016–11020.

    Article  PubMed  CAS  Google Scholar 

  12. MCGILLIVRAY MH AND, MCGILLIVRAY B.: Hypogonadism and chromosomal disorders. In: Lifshits F eds. Pediatric Endocrinology. New York, Marcel Dekker, 1990, 377–412.

    Google Scholar 

  13. MENDEZ JP, ULLOA-AGUIRRE A, KOFMAN-ALFARO S, ET AL.: Mixed gonadal dysgenesis: clinical, cytogenetic, endocrinological and histopathological findings in 16 patients. Am. J. Med. Genet, 1993, 46: 263–267.

    Article  PubMed  CAS  Google Scholar 

  14. OGATA T, HAWKINS JR, TAYLOR A, ET AL.: Sex reversal in a child with a 46, Y, Xp+karyotype: support for the existence of a gene(s), located in distal Xp, involved in testis formation. J. Med. Genet 1992, 29: 226–230.

    Article  PubMed  CAS  Google Scholar 

  15. PELLETIER J, BRUENING W, KASHTAN CE, ET AL.: Germline mutations in Wilm’s tumor suppressor gene are associated with abnormal urogenital development in Denys-Drash syndrome. Cell, 1991, 67: 437–447.

    Article  PubMed  CAS  Google Scholar 

  16. POULAT F, MORIN D, KÖNIG A, ET AL.: Distinct molecular origins for Denys-Drash and Frasier syndromes. Hum. Genet, 1993, 91: 285–286.

    Article  PubMed  CAS  Google Scholar 

  17. SULTAN C, LOBACCARO JM, MEDLEJ R, POULAT F AND BERTA P.: SRY and male sex determination. Horm. Res, 1991, 36: 1–3.

    Article  PubMed  CAS  Google Scholar 

  18. TOMMERUP N, SCHEMPP W, MEINECKE P, ET AL.: Assignement of an autosomal sex reversal locus (SRA1) and campomelic dysplasia (CMPD1) to 17q24.3-q25.1. Nature Genet, 1993, 4: 170–174.

    Article  PubMed  CAS  Google Scholar 

  19. VILAIN E, JAUBERT F, FELLOUS M AND MCELREAVEY K.: Pathology of 46, XY pure gonadal dysgenesis: absence of testis differentiation associated with mutations in the testis-determining factor. Differentiation, 1993, 52: 151–159.

    Article  PubMed  CAS  Google Scholar 

  20. VILAIN E, MCELREAVEY K, VIDAUD M, RICHAUD F AND FELLOUS M.: L’analyse de SRY n’explique pas toute la pathologie du déterminisme du sexe. Ann. Endocrinol. (Paris), 1991, 52: 435–436.

    CAS  Google Scholar 

  21. WILKIE AOM, CAMPBELL FM, DAUBENEY P, ET AL.: Complete and partial XY sex reversal associated with terminal deletion of 10q — Report of 2 cases and literature review. Am. J. Med. Genet, 1993, 46: 597–600.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Unité de Biochimie Endocrinienne du Développement et de la Reproduction, Hôpital Lapeyronie et INSERM U58, Montpellier

    Ch. Sultan, S. Lumbroso & J. M. Lobaccaro

  2. Endocrino-Gynécologie Pédiatriques, Service de Pédiatrie 1, Hôpital Arnaud de Villeneuve, Montpellier

    Ch. Sultan

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Sultan, C., Lumbroso, S. & Lobaccaro, J.M. Génétique moléculaire des dysgénésies testiculaires. Androl. 4, 30–36 (1994). https://doi.org/10.1007/BF03034617

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Basic and Clinical Andrology

ISSN: 2051-4190