WT1

The WT1 gene provides instructions for making a protein that is involved in the development of the kidneys and gonads (ovaries in females and testes in males) before birth. The WT1 protein regulates the activity of other genes by attaching (binding) to specific regions of DNA. On the basis of this action, the WT1 protein is called a transcription factor. The WT1 protein plays a role in cell growth, the process by which cells mature to carry out specific functions (cell differentiation), and the self-destruction of cells (apoptosis).

cancers - associated with the WT1 gene

Some people with Wilms tumor (a rare form of kidney cancer) have a mutation in one copy of the WT1 gene in every cell. In other people with Wilms tumor, WT1 gene mutations are only present in the tumor cells. These changes are typically somatic, which means they are acquired during a person's lifetime. Wilms tumor usually develops in children by the age of 3 or 4 although adult onset cases have occurred. Approximately 25 percent of people with Wilms tumor will experience abdominal pain, fever, a shortage of red blood cells (anemia), blood in the urine (hematuria), and high blood pressure (hypertension).

Changes in the activity (expression) of the WT1 gene are associated with several other forms of cancer. In particular, the WT1 gene is abnormally expressed in certain types of lung, prostate, breast, and ovarian cancer. Abnormal expression of the WT1 gene is also seen in some cancers of blood-forming cells (leukemias), such as acute lymphoblastic leukemia (ALL), chronic myeloid leukemia (CML), and childhood acute myeloid leukemia (AML). It is unclear what role the WT1 protein plays in the development or progression of cancer.

Wilms tumor, aniridia, genitourinary anomalies, and mental retardation syndrome - associated with the WT1 gene

The WT1 gene is located in a region of chromosome 11 that is often deleted in people with Wilms tumor, aniridia, genitourinary anomalies, and mental retardation syndrome, more commonly known by the acronym WAGR syndrome. As a result of this deletion, affected individuals are missing one copy of the WT1 gene in each cell. The loss of this gene is responsible for the genitourinary abnormalities and the increased risk of Wilms tumor in affected individuals.

other disorders - caused by mutations in the WT1 gene

Mutations in the WT1 gene can cause a condition called Denys-Drash syndrome. This condition is characterized by kidney (renal) disease, Wilms tumor, and in individuals with a typical male chromosome pattern (46, XY), external genitalia that do not look clearly male or female (ambiguous genitalia). Females with Denys-Drash syndrome have normal female genitalia. Renal disease usually occurs before age 2, leading to life-threatening renal failure and end-stage renal disease (ESRD) before age 4. Most WT1 gene mutations that cause Denys-Drash syndrome change single DNA building blocks (nucleotides) in one of two areas of the gene known as exon 8 or exon 9. These mutations impair the WT1 protein's ability to bind to DNA. Most cases of Denys-Drash syndrome are not inherited, but are the result of a new mutation.

WT1 gene mutations can also cause a condition called Frasier syndrome. Most mutations disrupt the way the WT1 gene's instructions are used to make the protein. These WT1 mutations result in a shortage of functional protein. Affected individuals with a typical male chromosomal pattern (46, XY) have female external genitalia. They also have no functional gonads (ovaries or testes), but instead have underdeveloped clumps of tissue called streak gonads. These abnormal gonads often become cancerous, so they are usually removed surgically early in life. Females with Frasier syndrome typically have normal genitalia and gonads. People with Frasier syndrome also develop progressive renal disease and may have scarring of the blood vessels within the kidneys (glomerular sclerosis). Life threatening ESRD typically occurs during adolescence.