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Keywords:

  • androgen receptor;
  • AR;
  • AIS;
  • prostate cancer;
  • genotype–phenotype

Abstract

The current version of the androgen receptor gene (AR) mutations database is described. A major change to the database is that the nomenclature and numbering scheme now conforms to all Human Genome Variation Society norms. The total number of reported mutations has risen from 605 to 1,029 since 2004. The database now contains a number of mutations that are associated with prostate cancer (CaP) treatment regimens, while the number of AR mutations found in CaP tissues has more than doubled from 76 to 159. In addition, in a number of androgen insensitivity syndrome (AIS) and CaP cases, multiple mutations have been found within the same tissue samples. For the first time, we report on a disconnect within the AIS phenotype–genotype relationship among our own patient database, in that over 40% of our patients with a classic complete AIS or partial AIS phenotypes did not appear to have a mutation in their AR gene. The implications of this phenomenon on future locus-specific mutation database (LSDB) development are discussed, together with the concept that mutations can be associated with both loss- and gain-of-function, and the effect of multiple AR mutations within individuals. The database is available on the internet (http://androgendb.mcgill.ca), and a web-based LSDB with the variants using the Leiden Open Variation Database platform is available at http://www.lovd.nl/AR. Hum Mutat 33:887–894, 2012. © 2012 Wiley Periodicals, Inc.