A genetic condition where affected people have male chromosomes and male gonads with complete or partial feminization of the external genitals
An inherited X-linked recessive disease with a mutation in the Androgen Receptor (AR) gene resulting in:
Functioning Y sex chromosome
Abnormality on X sex chromosome
CAIS (completely insensitive to AR gene)
External female genitalia
Lacking female internal organs
PAIS (partially sensitive-varying degrees)
External genitalia appearance on a spectrum (male to female)
MAIS (mildly sensitive, rare)
Impaired sperm development and/or impaired masculinization
Also called Testicular Feminization
Affects 1 in 20,400 people
2/3 of cases inherited from mother
1/3 of cases come from a spontaneous mutation in the egg
No effect on life expectancy
For a carrier woman, there is a 1 in 4 chance in each pregnancy that the child will have AIS and a 1 in 2 chance if the fetus is male
No racial differences
Androgen Receptor Gene
AIS results from mutations in the androgen receptor gene, located on the long arm of the X chromosome (Xq11-q12).
The AR gene provides instructions to make the protein called androgen receptor, which allows cells to respond to androgens, such as testosterone, and directs male sexual development.
Androgens also regulate hair growth and sex drive
Mutations include complete or partial gene deletions, point mutations and small insertions or deletions.
The Process of Sexual Development
In AIS the chromosome sex and gonad sex do not agree with the phenotypic sex
Phenotypic sex results from secretions of hormones from the testicles
The two main hormones secreted from the testicles are testosterone and mullerian duct inhibitor
Testosterone is converted into dyhydrotestosterone
Mullerian duct inhibitor suppresses the mullerian ducts and prevents the development of internal female sex organs in males
Wolffian ducts help develop the rest of the internal male reproductive system and suppress the Mullerian ducts
Defective androgen receptors cause the wolffian ducts and genitals to be unable to respond to the androgens testosterone and dihydrotestosterone.