CYP19A1 gene

The CYP19A1 gene provides instructions for making the aromatase enzyme, which is essential for converting androgens into estrogen and regulating sexual development and bone growth.

Normal Function

The CYP19A1 gene provides instructions for making an enzyme called aromatase. This enzyme converts a class of hormones called androgens, which are involved in male sexual development, to different forms of the female sex hormone estrogen.

In cells, aromatase is found in a structure called the endoplasmic reticulum, which is involved in protein production, processing, and transport. The activity (expression) of aromatase varies among different cell types depending on the cells' need for estrogen. In females, aromatase is most active in the ovaries, where it guides sexual development. In males, aromatase is most active in fat (adipose) tissue. In both males and females, estrogen plays a role in regulating bone growth and blood sugar (glucose) levels. During fetal development, aromatase converts androgens to estrogens in the placenta, which is the link between the mother's blood supply and the fetus. This conversion in the placenta prevents androgens from directing sexual development in female fetuses. After birth, the conversion of androgens to estrogens takes place in multiple tissues.

Health Conditions Related to Genetic Changes

Aromatase deficiency

More than 20 mutations in the CYP19A1 gene have been found to cause aromatase deficiency. This condition is characterized by reduced levels of estrogen and increased levels of androgens. These abnormal hormone levels lead to impaired sexual development in affected females and unusual bone growth, insulin resistance, and other signs and symptoms in both males and females with the condition. CYP19A1 gene mutations that cause aromatase deficiency decrease or eliminate aromatase activity. A lack of aromatase function results in an inability to convert androgens to estrogens before birth and throughout life. In women who are pregnant with an affected fetus, excess androgens in the placenta pass into the woman's bloodstream, and may cause her to have temporary signs and symptoms of aromatase deficiency.

Aromatase excess syndrome

More than 10 rearrangements of genetic material involving the CYP19A1 gene have been found to cause aromatase excess syndrome. This condition is characterized by the increased conversion of androgens to estrogen. As a result, affected males have enlarged breasts (gynecomastia) and short stature; affected females can have irregular menstrual periods and short stature.

Several types of genetic rearrangement involving the CYP19A1 gene can cause aromatase excess syndrome:

• Duplications: Some genetic rearrangements duplicate parts of the CYP19A1 gene, doubling some of the instructions used for making the enzyme, resulting in more enzyme than normal.
• Deletions: These remove parts of the CYP19A1 gene and a nearby gene. The remaining DNA is fused together, creating a fusion gene. These fusion genes cause the CYP19A1 gene to be active in tissues where it is not normally expressed, leading to increased aromatase production.
• Inversions: DNA is broken in two places, reversed, and reinserted into the chromosome. Inversions involving the CYP19A1 gene and a nearby gene also result in the production of a fusion gene, leading to increased aromatase production.

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