Functional Impact of Novel Androgen Receptor Mutations on the Clinical Manifestation of Androgen Insensitivity Syndrome.
作者： Reginaldo J. Petroli , Olaf Hiort , Dagmar Struve , Julia K. Gesing , Fernanda C. Soardi
DOI: 10.1159/000484882
关键词:
摘要: Androgens are responsible for the development and maintenance of male sex characteristics. Dysfunctions in androgen action due to mutations receptor gene (AR) can lead insensitivity syndrome (AIS) that be classified as mild (MAIS), partial (PAIS), or complete (CAIS). We have analyzed functional effects p.Ser760Thr, p.Leu831Phe, p.Ile899Phe, p.Leu769Val, p.Pro905Arg combination p.Gln799Glu + p.Cys807Phe were identified patients with PAIS CAIS. The p.Leu769Val showed disruption AR under physiological hormone concentrations; however, they differed high DHT concentrations especially N/C terminal interaction assay. Mutations p.Ile899Phe presented transactivation activities higher than 20% wild type increased concentrations. However, each one a different profile When combination, <10% physiologic conditions indicated an association CAIS phenotype. conclude analysis elucidated role mutant ARs, giving clues molecular mechanisms associated clinical AIS manifestations. Differences hormone-dependent profiles may provide basis response treatment particular case.
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