title: Male infertility and androgen receptor gene mutations: clinical features and identification of seven novel mutations.
abstract: OBJECTIVE
  Androgens and a functioning androgen receptor (AR) are essential for development and maintenance of the male phenotype and spermatogenesis. Consistent with this, mutations in the AR gene cause a variety of defects related to androgen insensitivity, ranging from complete feminization to phenotypic males with infertility. The aim of his study was to analyse the prevalence of AR gene mutations in male infertility and to clarify the genotype-phenotype relation.
  
  
  METHODS
  Males with infertility were recruited consecutively at the Centre for Male Gamete Cryopreservation at the University of Padova from January 1996 to January 2005.
  
  
  METHODS
  One thousand five hundred and seventeen men with < 10 million sperm/ml and 310 age-matched normozoospermic controls.
  
  
  METHODS
  Screening for AR gene mutation was done by DHPLC and sequencing, and reproductive hormone concentrations were measured.
  
  
  RESULTS
  We found 20 mutations in 26 of 1517 patients (1.7%) and no mutations in controls. A high number of mutations localized in exon 1 of the AR gene coding for the transactivation domain of the protein. Of 20 mutations, 7 represent novel mutations. With respect to men without AR mutations, subjects with AR mutations have lower ejaculate volume, higher testosterone levels, higher oestradiol levels, and higher androgen sensitivity index. However, the ranges for these variables were highly overlapping between men with and without AR gene mutations. Also clinical manifestations of AR mutations are not unique and 22 men had only spermatogenic impairment.
  
  
  CONCLUSIONS
  AR gene mutations are quite frequent in unselected infertile men but no specific hormonal or clinical data could be used to preselect patients at risk of mutations.
authors.affiliation: University of Padova, Department of Histology, Microbiology and Medical Biotechnologies, Centre for Male Gamete Cryopreservation, Padova, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Ferlin
authors.forename: Cinzia
authors.initials: C
authors.lastname: Vinanzi
authors.forename: Andrea
authors.initials: A
authors.lastname: Garolla
authors.forename: Riccardo
authors.initials: R
authors.lastname: Selice
authors.forename: Daniela
authors.initials: D
authors.lastname: Zuccarello
authors.forename: Carla
authors.initials: C
authors.lastname: Cazzadore
authors.forename: Carlo
authors.initials: C
authors.lastname: Foresta
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D004958:Estradiol / Q000097:blood; D005640:Follicle Stimulating Hormone / Q000097:blood; D015870:Gene Expression; D005838:Genotype; D006801:Humans; D007248:Infertility, Male / Q000235:genetics* / Q000378:metabolism; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D009154:Mutation; D009845:Oligospermia / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D011944:Receptors, Androgen / Q000235:genetics* / Q000378:metabolism; D013076:Sperm Count; D018709:Statistics, Nonparametric; D013739:Testosterone / Q000097:blood
chemical_list: D011944:Receptors, Androgen; D013739:Testosterone; D004958:Estradiol; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone