Androgen Insensitivity Syndrome

The AR gene is located on the long arm of the X chromosome, at a location that is designated as Xq11-q12. The gene is about 90,000 nucleotides Testosterone from the testis binds to the androgen receptor. This complex then triggers gene expression. Mutation in the receptor prevents either testosterone binding (a), DNA binding (b), or some other activity. long, though fewer than 3,000 of these actually code for amino acids in the protein. The protein formed from the gene has different domains that perform different functions. One region binds testosterone, another regulates the movement of the complex to the nucleus, and a third binds the complex to the DNA. Other regions, some overlapping, control other functions.

Mutations to the coding portion for any one of these domains can prevent the receptor complex from functioning properly. All known mutations in the AR gene cause a loss of function and exhibit the recessive inheritance pattern. A male carries only one X chromosome, and receives only one copy of the AR gene. If this gene is mutated, the male will have androgen insensitivity syndrome.

Women with one mutated AR gene will not exhibit the syndrome but instead will be carriers, whose male children have a 50 percent risk of inheriting the mutant gene. Since affected individuals are sterile, they cannot pass it on to offspring. It is believed that about one-third of all cases are due to new mutations, which are not present in the mother's genes but which arise in the development of the early embryo. Genetic testing is available for women who desire children but who have a family history of androgen insensitivity. For women who are carriers, prenatal testing is available to determine if a fetus has inherited the mutant gene.