Androgen insensitivity syndrome
Causes
What mutation causes androgen insensitivity syndrome?
Androgen insensitivity syndrome is caused by mutations, or changes, in the AR, or androgen receptor gene. The AR gene is located on the X chromosome. These changes are typically small genetic changes, known as single base substitutions or deletions. Sometimes, however, larger changes (deletions and duplications) in the gene have also been found within the gene.
The AR gene gives the body instructions for making androgen receptors, which allow cells to respond to androgens, such as testosterone. When the AR gene is working properly, the receptors work properly, and normal male development should occur. In androgen insensitivity syndrome (AIS), a genetic change in the AR gene causes the gene to not work properly. Therefore, these receptors are either not made, or are made but do not work as well as they should. The body produces the correct amount of androgens; however, the cells are unable to respond to the hormones since there are no receptors.
Individuals with AIS are born as chromosomal males (46, XY). This means that they are genetically male, with an X and a Y chromosome, but have female characteristics (feminization) of their sexual organs. They also experience a lack of secondary sexual development, and infertility problems. There are three main types of this syndrome: complete, partial, and mild. Each of these types has different signs and symptoms.
To learn more about the genes involved, talk to your doctor or seek genetic counseling. Genetic counselors can be found on the National Society of Genetic Counselors website.
More Causes Content
Do some genetic changes make androgen insensitivity syndrome worse?
Why are androgens important to the body like in androgen insensitivity syndrome?
Do some genetic changes make androgen insensitivity syndrome worse?
Greater than 600 genetic changes, also called mutations, have been identified in the AR gene that cause androgen insensitivity syndrome. Different changes will have different effects on the severity of the disorder.
Some mutations in the AR gene cause the androgen receptor to not work at all. This means that there are no androgen receptors produced at all. In these cases, an individual cannot respond to any amount of hormone (androgen). When this occurs, it is called complete androgen insensitivity syndrome (AIS).
Other mutations in the AR gene can reduce, but still retain partial functioning of the receptor. This means that there are some androgen receptors produced and the individual can respond to some hormone (androgen). These cases are called partial AIS.
Finally, some mutations have little effect the functioning of the androgen receptor. This means that there are some androgen receptors produced and the individual can respond to some hormone (androgen). These cases are called mild AIS. The difference between partial and mild AIS are the amount of receptors produced. There are more receptors produced in mild AIS, meaning that the body has more response to hormone (androgen) and is therefore less affected.
To learn more about the genetic changes that cause AIS, talk to your doctor or a genetic counselor. Genetic counselors can be found on the National Society of Genetic Counselors website.
References
Are genetic changes in the AR gene a predisposition (tendency) or a cause of androgen insensitivity syndrome?
Mutations, or changes, within the AR gene are causes for androgen insensitivity syndrome. Mutations in the AR gene are not just a predisposition, which is only a tendency to have a certain condition.
To learn more about the genetic changes that cause AIS, talk to your doctor or a genetic counselor. Genetic counselors can be found on the National Society of Genetic Counselors website.
References
Why are androgens important to the body like in androgen insensitivity syndrome?
Androgens are a group of hormones that are produced by both males and females. They are important in male and female bodies. They play an important role in the hormone pathway of development of male characteristics and reproductive activity. The main androgens produced are testosterone and androstenedione. These hormones in particular play are large part in developing male characteristics as a fetus and during puberty. If there are not enough androgens, individuals develop as female. Also, in the case of AIS, if there are enough androgens, but the body cannot detect or respond to them, individuals develop as female. Typically, in females, androgens play more subtle roles. In both males and females, androgens and their receptors also help to regulate hair growth and sex drive.
Androgen insensitivity syndrome (AIS) occurs when the cells that make up the body are unable to respond to androgens. Individuals with AIS are born as chromosomal males (46, XY), meaning that they are genetically male, with feminization (female characteristics) of their sexual organs, a lack of secondary sexual development, and infertility problems.There are three main types of this syndrome: complete, partial, and mild. Each of these types has different signs and symptoms.
To learn more about androgens, visit: Androgens
