title: A novel mutation in the D-box of the androgen receptor gene (S597R) in two unrelated individuals Is associated with both normal phenotype and severe PAIS.
abstract: BACKGROUND
  An absent or dysfunctional androgen receptor (AR) in 46,XY individuals is the most common cause of various degrees of undermasculinization. Therefore, we routinely perform sequencing of the AR gene in all cases with suspected androgen insensitivity.
  
  
  METHODS
  In a newborn 46,XY male diagnosed with partial androgen insensitivity syndrome and a phenotypically normal man, who in childhood had bilateral cryptorchidism, the AR was directly sequenced. Seven additional men with cryptorchidism in infancy were chosen as controls.
  
  
  RESULTS
  An AR variant (S597R) was identified in both males. Treatment of the newborn with 1% dihydrotestosterone ointment locally, resulted in normal penile size for age. Sequencing of the region in 7 other men with cryptorchidism in infancy did not reveal any additional deviation from the normal reference sequence.
  
  
  CONCLUSIONS
  The same mutation at this codon can cause significantly different phenotypes as shown by the variation in masculinization of these individuals, with 1 severely affected child and 1 normally developed man. However, the S597R mutation does not seem to be a common cause of undescended testes in boys. Despite the S597R mutation and severe undermasculinization, as seen in the baby, normal male phenotype for age could be achieved with treatment.
authors.affiliation: Department of Urology, Malmö University Hospital, Lund University, Malmö, Sweden. Yvonne.Giwercman@kir.mas.lu.se
authors.forename: Yvonne L
authors.initials: YL
authors.lastname: Giwercman
authors.forename: Sten A
authors.initials: SA
authors.lastname: Ivarsson
authors.forename: Jonas
authors.initials: J
authors.lastname: Richthoff
authors.forename: Kristina B
authors.initials: KB
authors.lastname: Lundin
authors.forename: Aleksander
authors.initials: A
authors.lastname: Giwercman
mesh_terms: D000293:Adolescent; D019943:Amino Acid Substitution; D013734:Androgen-Insensitivity Syndrome / Q000235:genetics*; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D020125:Mutation, Missense / Q000235:genetics*; D010641:Phenotype; D011944:Receptors, Androgen / Q000235:genetics*
chemical_list: D011944:Receptors, Androgen