Nephrotic type 4 syndrome - WT1 gene
Nephrotic syndrome type 4 (NPHS4), is a renal disease characterized by an increased permeability of the capillary walls of the glomerulus, causing the inability of the kidneys to control the function of glomerular filtration. As a result, high concentrations of protein in urine, decreased blood protein levels, ascites, edema, and ultimately, renal insufficiency appear.
Signs and symptoms of the disease include proteinuria, hypoproteinemia, edema, diffuse mesangial sclerosis and diffuse glomerulosclerosis, focal and segmental. Some affected individuals develop Wilms tumor. Others have genitourinary anomalies.
This process is due to mutations in the WT1 gene, located on the short arm of chromosome 11 (11p13) which encodes a protein necessary for the development of kidney and gonads protein. Within these tissues, the protein plays a role in cell growth and differentiation, and apoptosis. To perform these functions, the WT1 protein regulates the activity of other genes by binding to specific regions of DNA. Based on this action, the WT1 protein is called a transcription factor.
Most mutations in WT1 gene are located in the exosnes 8 and 9. These mutations impair the ability of the protein to bind to DNA.
This disease is inherited in an autosomal recessive pattern, that is, both copies of the gene in every cell must have mutations for alteration is expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually show no signs and symptoms of the disease.
Tests in IVAMI: in IVAMI perform detection of mutations associated with nephrotic syndrome type 4, by complete PCR amplification of the exons of the WT1 gene, and subsequent sequencing.
Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).