PITX1 gene
The PITX1 gene provides essential instructions for the development of the legs and feet, and mutations in this gene are linked to various limb and skeletal disorders.
Normal Function
The PITX1 gene provides instructions for making a protein that plays a critical role in the development of the legs and feet. The protein acts as a transcription factor, which means that it binds to specific regions of DNA and helps control the activity of particular genes. Specifically, the PITX1 protein regulates the activity of genes that direct the development of the bones and tissues in the legs, knees, ankles, and feet.
The PITX1 protein is also found in the embryonic structures called branchial arches that give rise to tissues in the face and neck and in the developing pituitary gland, which is a hormone-producing gland located at the base of the brain. Researchers suspect that the PITX1 protein may play a role in the formation of the pituitary gland and in the formation of certain tissues that are derived from the branchial arches, such as the roof of the mouth, the jaw, and parts of the inner ear.
Health Conditions Related to Genetic Changes
Liebenberg syndrome
Changes in the long arm (q) of chromosome 5 that affect the PITX1 gene cause Liebenberg syndrome. This condition is characterized by the abnormal development of the elbows, wrists, and hands. Affected individuals typically have joint deformities called contractures that limit the movement of these structures.
People with Liebenberg syndrome have deletions, insertions, or rearrangements of the long arm of chromosome 5 that affect regions of DNA known as regulatory elements. These regulatory elements help turn genes on (enhancers) or off (repressors) during development. The chromosome changes that cause Liebenberg syndrome typically move an enhancer that activates the genes that are involved in the development of the arms and hands closer to the PITX1 gene.
As a result of these changes, the PITX1 gene is abnormally active when the arms and hands are developing. Because the PITX1 protein normally directs the development of the legs and feet, the bones and tissues in the arms and hands develop more like those in the legs and feet.
Other disorders
Changes in the PITX1 gene have been found to cause an inward- and upward-turning foot (clubfoot) with or without the absence or severe shortening of a bone in the lower leg called the tibia (tibial hemimelia). Some individuals also have extra toes (polydactyly) arranged such that the outer toes are mirror images of the inner toes; this condition is called mirror-image polydactyly. Unlike in Liebenberg syndrome, these features are caused by changes in the PITX1 gene itself. These changes cause cells to produce fewer functional PITX1 proteins, which disrupts the normal development of the legs, feet, and toes.
Other Names for This Gene
- BFT
- paired-like homeodomain 1
- paired-like homeodomain transcription factor 1
- pituitary homeobox 1
- pituitary otx-related factor
- POTX
- PTX1