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Syndromes d’insensibilite aux androgenes: Aspects moleculaires

Androgen insensitivity: Molecular aspects

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Abstract

The molecular analysis of clinical syndromes involving androgen insensitivity has been facilitated by the availability of increasingly powerful molecular biological techniques. Complementary DNA of the androgen receptor gene (wich was recently cloned and sequenced) has been used as a probe to investigate DNA restriction fragment length polymorphisms in patients with partial or complete androgen insensitivity. Such studies have demonstrated that deletions are rare. Using enzymatic amplification and sequencing of exons of the androgen receptor gene, several groups have described point mutations in patients with androgen insensitivity. PCR, accompanied by denaturing gradient gel electrophoresis or single strand conformation polymorphism assays, has revealed further mutations. These powerful tools, together with studies of mRNA from expression of the mutant gene, have also illustrated structure-function associations of the androgen receptor gene in some patients with androgen insensitivity.

Resume

L’analyse moléculaire des syndromes d’insensibilité aux androgènes est aujourd’hui facilitée par l’utilisation d’outils de génétique moléculaire de plus en plus performants: polymorphismes de restriction, amplification enzymatique, polymorphisme de conformation des simples brins d’ADN, séquençage et expression des gènes mutés. Les différentes études ont souligné le caractère exceptionnel des délétions du gène du récepteur des androgènes et ont permis la détection de mutation géniques responsables de l’insensibilité aux androgènes. L’étude de l’ARN messager a également montré une anomalie de l’épissage chez un patient porteur d’une insensibilité complète aux androgènes. Enfin, l’analyse des produits d’expression des gènes mutés produits in vitro a permis d’établir dans certains cas un rapport structure-fonction.

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Correspondence to Charles Sultan.

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Sultan, C., Lobaccaro, J.-., Lumbroso, S. et al. Syndromes d’insensibilite aux androgenes: Aspects moleculaires. Androl. 2, 108–113 (1992) doi:10.1007/BF03034686

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Key-words

  • Androgen insensitivity
  • androgen receptor
  • RFLP
  • SSCP
  • point mutations
  • molecular genetics

Motsclés

  • Insensibilités aux androgènes
  • récepteur des androgènes
  • RFLP
  • SSCP
  • mutations ponctuelles
  • génétique moléculaire