Missense Mutation in the Ligand-Binding Domain of the Horse Androgen Receptor Gene in a Thoroughbred Family with Inherited 64,XY (SRY+) Disorder of Sex Development

Disorders of sex development (DSD) have long been documented in domestic animal species including horses. However, there is only a single report of an androgen receptor (AR) mutation causative of such a DSD syndrome in a horse pedigree. Here, we present a new familial AR mutation in horses. A missense mutation (c.2042G>C) at AR exon 4 explains the segregation of the DSD in a Thoroughbred horse pedigree. The mutation, expected to affect the ligand-binding domain of the AR protein, led to complete androgen insensitivity of 64,XY SRY+, testicular DSD individuals. Additionally, the design of a PCR-RFLP technique provided an accurate molecular test for the identification of horses carrying the mutation.