title: A novel mutation c.118delA in exon 1 of the androgen receptor gene resulting in complete androgen insensitivity syndrome within a large family.
abstract: OBJECTIVE
  To confirm the clinical diagnosis of complete androgen insensitivity syndrome (CAIS) by molecular genetic testing and to offer carriership testing in female relatives should a disease-causing mutation be found.
  
  
  METHODS
  Case report.
  
  
  METHODS
  University hospital.
  
  
  METHODS
  Caucasian family in which two sisters were clinically diagnosed with CAIS during childhood.
  
  
  METHODS
  Molecular genetic testing of the androgen receptor (AR) gene.
  
  
  METHODS
  Genetic counseling in affected and unaffected female family members.
  
  
  RESULTS
  Identification of a novel mutation in exon 1 of the AR gene, c.118delA. This frameshift mutation (p.R40fs174ter) is located in the N-terminal transactivation domain and leads to a predicted truncated protein of 173 amino acids with loss of the major part of the N-terminal transactivation domain, and the DNA-binding and ligand-binding domain. Segregation analysis showed carriership of this mutation in the mother and two sisters.
  
  
  CONCLUSIONS
  In agreement with functional studies of other AR gene mutations located in the N-terminal transactivation domain, this novel mutation c.118delA is presumed to result in a complete loss of AR function and to be associated with CAIS. Our study extends the spectrum of exon 1 mutations in the AR gene leading to CAIS. Molecular genetic testing of CAIS is recommended not only for diagnostic purposes in affected individuals but also for carriership testing and genetic counseling in unaffected female family members.
authors: Department of Endocrinology, Ghent University Hospital, Ghent, Belgium; Department of Urology, Ghent University Hospital, Ghent, Belgium.
authors: Karel
authors: K
authors: Decaestecker
authors: Service d'Hormonologie, CHU Lapeyronie, Montpellier, France.
authors: Pascal
authors: P
authors: Philibert
authors: Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium.
authors: Elfride
authors: E
authors: De Baere
authors: Department of Urology, Ghent University Hospital, Ghent, Belgium.
authors: Piet
authors: P
authors: Hoebeke
authors: Department of Endocrinology, Ghent University Hospital, Ghent, Belgium.
authors: Jean-Marc
authors: JM
authors: Kaufman
authors: INSERM U540, Endocrinologie Moléculaire et Cellulaire des Cancers and Service d'Hormonologie du Développement et de la Reproduction, CHU Montpellier, Montpellier, France.
authors: Charles
authors: C
authors: Sultan
authors: Department of Endocrinology, Ghent University Hospital, Ghent, Belgium. Electronic address: guy.tsjoen@ugent.be.
authors: Guy
authors: G
authors: T'Sjoen
mesh_terms: D013734:Androgen-Insensitivity Syndrome / Q000235:genetics*; D005091:Exons / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D011944:Receptors, Androgen / Q000235:genetics*
chemical_list: D011944:Receptors, Androgen