A novel mutation in the human androgen receptor suggests a regulatory role for the hinge region in amino-terminal and carboxy-terminal interactions.

Context: The androgen insensitivity syndrome (AIS) is caused by molecular defects in the androgen receptor (AR). Clinically, the partial AIS has a variable phenotype. Many mechanisms explain the phenotype in the AIS. A crucial step in AR action is the interaction of the N and C termini. Objective: The role of the hinge region of the AR is not as well understood as other parts of the receptor. We aim to study the role of this region in the N/C-termini interaction. Patient and Method: We report a patient with severe undermasculinization and poor response to exogenous androgens. Androgen binding was performed, and the AR gene was sequenced. The mutation was recreated and transfected in COS-1 cells. Transactivation was studied. N/C-termini interaction was studied using a mammalian two-hybrid assay. A nuclear localization study was performed. Results: Androgen binding was normal, and a novel mutation (Arg629Trp) in the AR hinge region was identified. Mutant AR transactivation was 40% higher compared with wild ...