Androgen Insensitivity Syndrome

Figure 1: Inheritance pattern of an X-linked, recessive allele.

Figure 2: A family tree of female carrier of AIS, her brother and sons with completely penetrant AIS.   

Androgen Insensitivity Syndrome (AIS)
OMIM #300068

Androgen Insensitivity Syndrome (AIS), formerly designated testicular feminization (TFM), is an X-linked recessive disorder affecting 46, XY males. AIS occurs in approximately 1 in 20,000 births and is the most common "male pseudohermaphroditism" (1). 
Individuals with AIS are unable to respond to androgens, testosterone (2). Phenotypically, AIS causes men to have such traits as external female genitalia, breast development, and a slight lack or total lack of hair on the body. Three forms of the syndrome with varying degrees of androgen insensitivity exist: complete androgen insensitivity (CAIS), partial androgen insensitivity (PAIS), and mild androgen insensitivity (MAIS).  

Figure 3: An individual who most likely has CAIS. Notice the lack of auxillary hair and breast development.

Androgen Receptor Gene
(Accession Number: from enterez-nucleotide: NG_009014, Gene ID: 376; from genecards: Gene ID: GC0XP066680)

Mutations in the androgen receptor, a.k.a. dihydrotestosterone receptor,cause all known forms of AIS as well as several other disorders. At present, approximately 400 mutations within the gene have been identified (1,2). Most of these mutations appear in the ligand binding domain. Often these mutations are base substitutions, causing either partial or mild AIS. In the case of insertions or deleltions resulting in an early stop codon, the more severe complete AIS is observed (1).

Figure 3: Depiction of androgen receptor gene and protein product
The gene contains eight exons.
The N-terminus domain (NTD) of the protein contains two polymorphic glutamine stretches. The protein contains a DNA binding domain (DBD) as well as a hinge region and ligand binding domain (LBD) (2).