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Genetics Home Reference: your guide to understanding genetic conditions
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WT1

Reviewed March 2013

What is the official name of the WT1 gene?

The official name of this gene is “Wilms tumor 1.”

WT1 is the gene's official symbol. The WT1 gene is also known by other names, listed below.

What is the normal function of the WT1 gene?

The WT1 gene provides instructions for making a protein that is necessary for the development of the kidneys and gonads (ovaries in females and testes in males). Within these tissues, the WT1 protein plays a role in cell growth, the process by which cells mature to perform specific functions (cell differentiation), and the self-destruction of cells (apoptosis). To carry out these functions, 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.

How are changes in the WT1 gene related to health conditions?

Denys-Drash syndrome - caused by mutations in the WT1 gene

At least 80 mutations in the WT1 gene have been found to cause Denys-Drash syndrome, a condition that affects development of the kidneys and genitalia and most often affects males. These mutations almost always occur in areas of the gene known as exon 8 and exon 9. Most mutations change single protein building blocks (amino acids) in the WT1 protein. The most common mutation that causes Denys-Drash syndrome (found in about 40 percent of cases) replaces the amino acid arginine with the amino acid tryptophan at protein position 394 (written Arg349Trp or R349W).

The mutations that cause Denys-Drash syndrome lead to the production of an abnormal WT1 protein that cannot bind to DNA. As a result, the activity of certain genes is unregulated, which impairs development of the kidneys and genitalia. Abnormal development of these organs leads to the signs and symptoms of Denys-Drash syndrome.

Rarely, a mutation in exon 8 or exon 9 of the WT1 gene causes a related condition called Frasier syndrome (described below). Because these two conditions share a genetic cause and have overlapping features, some researchers have suggested that these two conditions are part of a spectrum and not two distinct conditions.

Frasier syndrome - caused by mutations in the WT1 gene

At least seven mutations in the WT1 gene have been found to cause Frasier syndrome, a condition that affects development of the kidneys and genitalia and most often affects males. These mutations almost always occur in an area of the gene known as intron 9. The most common mutation that causes Frasier syndrome (found in over half of affected individuals) changes a single DNA building block (nucleotide) in the WT1 gene, written as IVS+4C>T. This mutation and others that cause Frasier syndrome alter the way the gene's instructions are pieced together to produce the protein.

The WT1 gene mutations that cause Frasier syndrome lead to the production of a protein with an impaired ability to control gene activity and regulate the development of the kidneys and reproductive organs, resulting in the signs and symptoms of Frasier syndrome.

Rarely, a mutation in intron 9 of the WT1 gene causes a related condition called Denys-Drash syndrome (described above). Because these two conditions share a genetic cause and have overlapping features, some researchers have suggested that these two conditions are part of a spectrum and not two distinct conditions.

cancers - associated with the WT1 gene

Mutations in the WT1 gene can cause Wilms tumor, a rare form of kidney cancer that usually occurs in early childhood. Some people with Wilms tumor have a mutation in one copy of the WT1 gene in every cell. Most of these are new mutations that occur during the formation of reproductive cells (eggs and sperm) or in early fetal development, although some may be inherited from a parent. In other people with Wilms tumor, WT1 gene mutations are present only in the tumor cells. These changes are typically somatic, which means they are acquired during a person's lifetime. WT1 gene mutations, whether they are somatic or present in every cell, account for 10 to 20 percent of cases of Wilms tumor.

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 also occurs 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

At least two mutations in the WT1 gene have been found to cause Meacham syndrome. This condition is characterized by abnormalities in the development of the male genitalia, heart, and diaphragm. Individuals with this condition have a typical male chromosome pattern (46,XY) but have external genitalia that do not look clearly male or clearly female (ambiguous genitalia) or have genitalia that appear completely female. Additionally, the internal reproductive organs are female, but they do not develop normally. Individuals with Meacham syndrome typically have heart defects that are present from birth and can vary in severity. They also have a hole in the muscle that separates the abdomen from the chest cavity (the diaphragm), which is called a congenital diaphragmatic hernia. Meacham syndrome is typically fatal in infancy. Approximately a dozen individuals have been described as affected with Meacham syndrome.

Mutations in the WT1 gene can also cause a condition called isolated nephrotic syndrome. This condition is characterized by an inability of the kidneys to filter waste products from blood, which leads to protein in the urine, swelling (edema), and ultimately, kidney failure. Isolated nephrotic syndrome includes diffuse glomerulosclerosis, in which scar tissue forms throughout the clusters of tiny blood vessels (glomeruli) in the kidneys, and focal segmental glomerulosclerosis, in which glomeruli in only certain areas of the kidneys experience scarring. Mutations in the WT1 gene most often cause diffuse glomerulosclerosis.

Where is the WT1 gene located?

Cytogenetic Location: 11p13

Molecular Location on chromosome 11: base pairs 32,387,774 to 32,435,534

The WT1 gene is located on the short (p) arm of chromosome 11 at position 13.

The WT1 gene is located on the short (p) arm of chromosome 11 at position 13.

More precisely, the WT1 gene is located from base pair 32,387,774 to base pair 32,435,534 on chromosome 11.

See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.

Where can I find additional information about WT1?

You and your healthcare professional may find the following resources about WT1 helpful.

You may also be interested in these resources, which are designed for genetics professionals and researchers.

What other names do people use for the WT1 gene or gene products?

  • WIT-2
  • WT1_HUMAN
  • WT33

See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What glossary definitions help with understanding WT1?

acids ; acute ; acute lymphoblastic leukemia ; acute myeloid leukemia ; amino acid ; AML ; apoptosis ; arginine ; cancer ; cell ; chromosome ; chronic ; congenital ; deletion ; differentiation ; DNA ; edema ; exon ; expressed ; gene ; genitalia ; hernia ; inherited ; intron ; kidney ; leukemia ; mental retardation ; motif ; mutation ; myeloid ; nucleotide ; ovarian ; progression ; prostate ; protein ; reproductive cells ; spectrum ; sperm ; syndrome ; testes ; tissue ; transcription ; transcription factor ; tryptophan ; tumor ; Wilms tumor

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • Andrade JG, Guaragna MS, Soardi FC, Guerra-Júnior G, Mello MP, Maciel-Guerra AT. Clinical and genetic findings of five patients with WT1-related disorders. Arq Bras Endocrinol Metabol. 2008 Nov;52(8):1236-43. (http://www.ncbi.nlm.nih.gov/pubmed/19169475?dopt=Abstract)
  • Ariyaratana S, Loeb DM. The role of the Wilms tumour gene (WT1) in normal and malignant haematopoiesis. Expert Rev Mol Med. 2007 May 24;9(14):1-17. Review. (http://www.ncbi.nlm.nih.gov/pubmed/17524167?dopt=Abstract)
  • Heathcott RW, Morison IM, Gubler MC, Corbett R, Reeve AE. A review of the phenotypic variation due to the Denys-Drash syndrome-associated germline WT1 mutation R362X. Hum Mutat. 2002 Apr;19(4):462. Review. (http://www.ncbi.nlm.nih.gov/pubmed/11933209?dopt=Abstract)
  • Miller-Hodges E, Hohenstein P. WT1 in disease: shifting the epithelial-mesenchymal balance. J Pathol. 2012 Jan;226(2):229-40. doi: 10.1002/path.2977. Epub 2011 Sep 29. Review. (http://www.ncbi.nlm.nih.gov/pubmed/21959952?dopt=Abstract)
  • Morrison AA, Viney RL, Ladomery MR. The post-transcriptional roles of WT1, a multifunctional zinc-finger protein. Biochim Biophys Acta. 2008 Jan;1785(1):55-62. Epub 2007 Oct 14. Review. (http://www.ncbi.nlm.nih.gov/pubmed/17980713?dopt=Abstract)
  • Morrison AA, Viney RL, Saleem MA, Ladomery MR. New insights into the function of the Wilms tumor suppressor gene WT1 in podocytes. Am J Physiol Renal Physiol. 2008 Jul;295(1):F12-7. doi: 10.1152/ajprenal.00597.2007. Epub 2008 Apr 2. Review. (http://www.ncbi.nlm.nih.gov/pubmed/18385267?dopt=Abstract)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/7490)
  • Niaudet P, Gubler MC. WT1 and glomerular diseases. Pediatr Nephrol. 2006 Nov;21(11):1653-60. Epub 2006 Aug 23. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16927106?dopt=Abstract)
  • OMIM: WT1 GENE (http://omim.org/entry/607102)
  • Suri M, Kelehan P, O'neill D, Vadeyar S, Grant J, Ahmed SF, Tolmie J, McCann E, Lam W, Smith S, Fitzpatrick D, Hastie ND, Reardon W. WT1 mutations in Meacham syndrome suggest a coelomic mesothelial origin of the cardiac and diaphragmatic malformations. Am J Med Genet A. 2007 Oct 1;143A(19):2312-20. (http://www.ncbi.nlm.nih.gov/pubmed/17853480?dopt=Abstract)
  • Yang L, Han Y, Suarez Saiz F, Minden MD. A tumor suppressor and oncogene: the WT1 story. Leukemia. 2007 May;21(5):868-76. Epub 2007 Mar 15. Review. Erratum in: Leukemia. 2007 Jul;21(7):1603. Saurez Saiz, F [corrected to Suarez Saiz, F]. (http://www.ncbi.nlm.nih.gov/pubmed/17361230?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: March 2013
Published: July 21, 2014