Detailed functional studies on androgen receptor mild mutations demonstrate their association with male infertility

@article{Zuccarello2008DetailedFS,
  title={Detailed functional studies on androgen receptor mild mutations demonstrate their association with male infertility},
  author={Daniela Zuccarello and Alberto Ferlin and Cinzia Vinanzi and Elisa Prana and Andrea Garolla and Leen Callewaert and Frank Claessens and Albert O. Brinkmann and Carlo Foresta},
  journal={Clinical Endocrinology},
  year={2008},
  volume={68}
}
Context   Mutations in the androgen receptor (AR) gene can cause the androgen insensitivity syndrome (AIS). For complete and severe partial AIS, well‐characterized in vitro functional assays can be used for genotype–phenotype correlation; however, for mild forms of AIS, as associated with male infertility, experimental evidence is scarce or lacking. In particular, optimal in vitro functional tests informative about the genotype–phenotype relation have not been described. 
Androgen insensitivity syndrome: clinical features and molecular defects
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This review focuses on the clinical features and molecular pathophysiology of AIS and explores the relationship of the molecular defects in the AR gene to their clinical expression.
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The del 57Leu mutation in the AR gene is a possible cause of idiopathic male infertility and the Ala474Val and Pro390Ser mutations might be significant markers for male infertility in Mediterranean populations.
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Management of androgen insensitivity syndrome should be undertaken by a multidisciplinary team and include gonadectomy to avoid gonad tumours in later life, appropriate sex-hormone replacement at puberty and beyond, and an emphasis on openness in disclosure.
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TLDR
Light is shed on the need to screen for mutations in the AR gene, causing male infertility whenever mild hypoandrogenic features are present with unexplained male infertility.
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  • Biology, Medicine
    Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology
  • 2013
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The prognosis for CAIS is good if the testicular tissue is removed at the appropriate time and for PAIS, the prognosis depends on the ambiguity of the genitalia and physical and psychosocial adjustment to the assigned sex.
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TLDR
The molecular study of the androgen receptor (AR) gene facilitated the understanding of the mechanism of CAIS and provided the genetic counselling clinically.
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Androgen insensitivity syndrome (AIS), previously known as testicular feminization, is an X‐linked recessive condition that results in failure of normal masculinization of the external genitalia in
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TLDR
Molecular analyses may be useful for genetic counseling of candidates with regard to the use of assisted reproductive techniques and might be responsible for some cases of idiopathic infertility, the present study suggested.
Role of Imaging in the Diagnosis and Management of Complete Androgen Insensitivity Syndrome in Adults
TLDR
Three cases of complete androgen insensitivity syndrome in adult women of 34, 22, and 38 years old are presented and imaging can be important both to diagnose the pathology and to localize gonads prior to surgical treatment.
In vitro functional characterization of androgen receptor gene mutations at arginine p.856 of the ligand-binding-domain associated with androgen insensitivity syndrome
TLDR
In a patient with complete AIS, a novel AR mutation p.R856 L is identified, which is associated with a spectrum of AIS phenotypes, and which is able to transactivate the (ARE)2-TATA promoter expressed in CHO cells more highly.
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