Denys-Drash syndrome ... (Denys-Drash syndrome) - Gen WT1
Syndrome Denys-Drash by of the association of severe nephropathy (glomerular mesangial sclerosis and early), Wilms tumor and gonadal dysgenesis resulting seudohermafrotidismo characterized. Kidney failure usually has an early onset before the age of five. The same applies to Wilms tumor, that eventually develop 90% of those affected by Denys-Drash syndrome, usually with an even earlier onset than usual, ie before 18 months. Although men with Denys-Drash syndrome of having the typical male chromosomes (46, XY) pattern, have gonadal dysgenesis with ambiguous genitalia or completely female genitalia. Testicles do not descend affected males, which means they are abnormally located in the pelvis, abdomen or groin. As a result, affected males are usually infertile. Meanwhile, affected women usually have normal genitals and show only renal disease characteristics. Because there are all associated features, they are usually diagnosed isolated nephrotic syndrome.
This process is due to point mutations in the WT1 gene, located on the short arm of chromosome 11 (11p13). This gene encodes a protein that is necessary for the development of kidney and gonads. Within these tissues, the WT1 protein plays a role in cell growth, cell 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.
They have identified at least 80 mutations in the WT1 gene in people with the syndrome Denys-Drash. These mutations occur almost always in exon 8 and exon 9 of WT1 gene. Most mutations change in individual amino acids of WT1 protein. The most frequent mutation causing syndrome Denys-Drash, found in about 40% of cases, replacing the amino acid arginine by tryptophan at position 394 of the protein (Arg349Trp R349W). Mutations causing syndrome Denys-Drash result encoding abnormal WT1 protein can not bind DNA. As a result, the activity of certain genes is unregulated, which affects development of the kidneys and of the genital organs. Rarely, a mutation in exon 8 or exon 9 of WT1 gene causes a disease related called Frasier syndrome - see Frasier syndrome ... -. Because these two diseases share a genetic cause and have overlapping characteristics, it is believed to be part of the same disease spectrum, not two different diseases.
Syndrome Denys-Drash is inherited as an autosomal dominant, which means that a copy of the altered gene in each cell is sufficient to express the disease.
Tests performed in IVAMI: in IVAMI perform detection of mutations associated with Denys-Drash syndrome, by complete PCR amplification of the exons of the WT1 gene, and subsequent secuenciación.Se recommended study initiation by exons 8 and 9 where most changes are localized, with possible reduction of time and cost involved in most cases. If not found the mutation in this region, it offers the ability to complete the study of the gene by amplification and sequencing of exons rest.
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).