title: Investigation of androgen receptor gene mutations in a series of 21 patients with 46,XY disorders of sex development.
abstract: OBJECTIVE
  Androgen receptor (AR) gene mutations are the leading cause of 46,XY disorders of sex development (DSD) and are associated with varying degrees of androgen insensitivity. The aim of this study is to investigate AR gene mutations in 46,XY DSD patients with normal testosterone secretion, either normal or high testosterone/dihydrotestosterone (T/DHT) ratio and normal SRD5A2 gene analysis, collectively, suggestive of androgen insensitivity syndrome (AIS).
  
  
  METHODS
  We direct sequenced all eight exons of the AR gene in 21 index patients with varying degrees of undervirilization.
  
  
  RESULTS
  We detected AR gene alterations in five patients. In patients with complete AIS we found p.Val30Met in exon 1 and p.Gly689* in exon 4. One patient with partial AIS had p.Gln712Glu in exon 4. In two patients with partial phenotype, we found common p.Glu213Glu (c.639G>A) SNP, and an additional p.Ile817Ile (c.2451T>C) mutation was found in one of these two patients.
  
  
  CONCLUSIONS
  Despite the fact that T/DHT ratio is frequently used in diagnosis of AIS, lack of precisely determined cutoffs compromises correct diagnosis. Hence, depending on clinical and biochemical findings solely may delay correct diagnosis. Direct sequence analysis of the AR is essential for precise diagnosis of AIS.
authors.forename: Vehap
authors.initials: V
authors.lastname: Topcu
authors.forename: Hatice
authors.initials: H
authors.lastname: Ilgin-Ruhi
authors.forename: Zeynep
authors.initials: Z
authors.lastname: Siklar
authors.forename: Halil Gurhan
authors.initials: HG
authors.lastname: Karabulut
authors.forename: Merih
authors.initials: M
authors.lastname: Berberoglu
authors.forename: Bulent
authors.initials: B
authors.lastname: Hacihamdioglu
authors.forename: Senay
authors.initials: S
authors.lastname: Savas-Erdeve
authors.forename: Zehra
authors.initials: Z
authors.lastname: Aycan
authors.forename: Havva Nur
authors.initials: HN
authors.lastname: Peltek-Kendirci
authors.forename: Gonul
authors.initials: G
authors.lastname: Ocal
authors.forename: Fatma Ajlan
authors.initials: FA
authors.lastname: Tukun
mesh_terms: D000293:Adolescent; D013734:Androgen-Insensitivity Syndrome / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D058490:Disorder of Sex Development, 46,XY / Q000235:genetics*; D005091:Exons; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009154:Mutation; D010641:Phenotype; D011944:Receptors, Androgen / Q000235:genetics*; D046468:Sexual Development / Q000235:genetics*; D013739:Testosterone
chemical_list: D011944:Receptors, Androgen; D013739:Testosterone