Wilms tumor 1 gene

WT1 is a zinc finger transcription factor, which acts as activator or repressor depending on the developmental or cellular context. Mutations of the gene result in disturbed genital development, Wilms tumour, and mesangial sclerosis.

Gene Structure

Four splice variants containing 10 and 9 exons have been identified. It may become more as upstream in in-frame with the first AUG, there is evidence of an other non-AUG (CUG) translation initiation site.

The promotor is GC-rich but does not contain a TATA box. SP1 binding sites have been identified and functionally confirmed. The promotor is probably used by an other gene, WIT1, that is transcribed in the opposite direction.

The mRNA is subject to tissue-restricted and developmentally regulated editing, which allows further fine tuning of cellular regulation processes.

Protein Structure

The funtioning transcription factor consists of four zinc-finger motifs at the C-terminus and a proline/glutamine-rich DNA-binding domain at the N-terminus.

Phenotype

Somatic mutations of the WT1 gene have been observed in a small number of Wilms tumors. Also, familial Wilms tumors are associated with heterozygous germline mutations, but most of these tumors an additional somatic mutation of the gene has been identified, indicating a second hit.

The WAGR syndrome was the first congenital disorder associated with this gene. The condition described by the features Wilms tumor, aniridia, urogenital malformations, and mental retardation is caused by truncating mutations often involving the downstream neighbor, the PAX6 gene.

Gene Regulation

The gene product, a zinc-finger transcription factor, controls normal development of the urogenital system. In podocytes it is essential to differentiation that includes the formation of a normal slit diaphragm.

Genetests:

Clinic	Method	Carrier testing
	Turnaround	5 days
	Specimen type	genomic DNA

Clinic	Method	Massive parallel sequencing
	Turnaround	25 days
	Specimen type	genomic DNA

Clinic	Method	Genomic sequencing of the entire coding region
	Turnaround	15 days
	Specimen type	genomic DNA

Clinic	Method	Multiplex Ligation-Dependent Probe Amplification
	Turnaround	20 days
	Specimen type	genomic DNA

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