Since it was not understood that these different presentations were all caused by the same set of mutations in the androgen receptor gene, a unique name was given to each new combination of symptoms, resulting in a complicated stratification of seemingly disparate disorders.Over the last 60 years, as reports of strikingly different phenotypes were reported to occur even among members of the same family, and as steady progress was made towards the understanding of the underlying molecular pathogenesis of AIS, these disorders were found to be different phenotypic expressions of one syndrome caused by molecular defects in the androgen receptor gene.AIS is now the accepted terminology for the syndromes resulting from unresponsiveness of the target cell to the action of androgenic hormones. CAIS encompasses the phenotypes previously described by "testicular feminization", Morris syndrome, and Goldberg-Maxwell syndrome; PAIS includes Reifenstein syndrome, Gilbert-Dreyfus syndrome, Lubs syndrome, "incomplete testicular feminization", and Rosewater syndrome; and MAIS includes Aimans syndrome.The more virilized phenotypes of AIS have sometimes been described as "undervirilized male syndrome", "infertile male syndrome", "undervirilized fertile male syndrome", etc., before evidence was reported that these conditions were caused by mutations in the AR gene. These diagnoses were used to describe a variety of mild defects in virilization; as a result, the phenotypes of some men who have been diagnosed as such are better described by PAIS (e.g. micropenis, hypospadias, and undescended testes), while others are better described by MAIS (e.g. isolated male infertility or gynecomastia).
In men, disease states are associated with extremes in polyglutamine tract length; prostate cancer, hepatocellular carcinoma, and intellectual disability are associated with too few repetitions, while spinal and bulbar muscular atrophy (SBMA) is associated with a CAG repetition length of 40 or more. Some studies indicate that the length of the polyglutamine tract is inversely correlated with transcriptional activity in the AR protein, and that longer polyglutamine tracts may be associated with male infertility and undermasculinized genitalia in men. However, other studies have indicated no such correlation exists. A comprehensive meta-analysis of the subject published in 2007 supports the existence of the correlation, and concluded these discrepancies could be resolved when sample size and study design are taken into account. Some studies suggest longer polyglycine tract lengths are also associated with genital masculinization defects in men. Other studies find no such association. AR mutations
As of 2010, over 400 AR mutations have been reported in the AR mutation database, and the number continues to grow. Inheritance is typically maternal and follows an X-linked recessive pattern; individuals with a 46,XY karyotype always express the mutant gene since they have only one X chromosome, whereas 46,XX carriers are minimally affected. About 30% of the time, the AR mutation is a spontaneous result, and is not inherited. Such de novo mutations are the result of a germ cell mutation or germ cell mosaicism in the gonads of one of the parents, or a mutation in the fertilized egg itself.