title: Novel and recurrent mutations in patients with androgen insensitivity syndromes.
abstract: OBJECTIVE
  Androgen insensitivity syndrome (AIS) caused by mutations within the androgen receptor gene represents a variety of phenotypes from females with 46,XY karyotype over individuals with ambiguous genitalia to infertile males.
  
  
  METHODS
  We studied 24 patients with AIS by sequencing androgen receptor gene. 19 of the investigated patients were affected by complete androgen insensitivity syndrome (CAIS) and 5 suffered from partial androgen insensitivity syndrome (PAIS).
  
  
  RESULTS
  So far we have detected 12 unreported mutations as well as 9 recurrent mutations (3 recurrent mutations were detected twice) in exons 2-8 of the androgen receptor gene. Three of the novel mutations cause a frameshift with subsequent premature termination and were found in patients with CAIS. These frameshifts were induced by single nucleotide deletion or insertion, or in one case by a 13-bp deletion, respectively. Another premature stop codon found in a CAIS patient results from an already reported nucleotide substitution in exon 5. Furthermore, in a CAIS patient we found a novel duplication of codon 788. All other mutations caused single base substitutions spread through exons 2-8 and were associated with CAIS or PAIS.
  
  
  CONCLUSIONS
  We report a broad spectrum of different mutations within the AR gene leading to various manifestations of AIS. Apart from truncating mutations, a reliable genotype/phenotype correlation cannot be established. Therefore, modifying factors must be effective.
authors.affiliation: Institut für Humangenetik der Otto-von-Guericke-Universität Magdeburg, Magdeburg, Germany. susanne.ledig@medizin.uni-magdeburg.de
authors.forename: Susanne
authors.initials: S
authors.lastname: Ledig
authors.forename: Sibylle
authors.initials: S
authors.lastname: Jakubiczka
authors.forename: Joseph
authors.initials: J
authors.lastname: Neulen
authors.forename: Ute
authors.initials: U
authors.lastname: Aulepp
authors.forename: Uta
authors.initials: U
authors.lastname: Burck-Lehmann
authors.forename: Klaus
authors.initials: K
authors.lastname: Mohnike
authors.forename: Hannelore
authors.initials: H
authors.lastname: Thiele
authors.forename: Hannelore
authors.initials: H
authors.lastname: Zierler
authors.forename: Carole
authors.initials: C
authors.lastname: Brewer
authors.forename: Peter
authors.initials: P
authors.lastname: Wieacker
mesh_terms: D000293:Adolescent; D000328:Adult; D013734:Androgen-Insensitivity Syndrome / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D004247:DNA / Q000737:chemistry / Q000235:genetics; D005260:Female; D016368:Frameshift Mutation; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011944:Receptors, Androgen / Q000235:genetics*; D017422:Sequence Analysis, DNA
chemical_list: D011944:Receptors, Androgen; D004247:DNA