Nephrotic type 8 syndrome - ARHGDIA gene.
Nephrotic syndrome type 8 (NPHS8) is a kidney disease clinically characterized by progressive renal insufficiency, severe proteinuria, hypoalbuminemia, hyperlipidemia and edema. Renal biopsies show diffuse mesangial sclerosis with small glomeruli, cellularity, increased extracellular matrix and surrounded glomeruli of abnormal or immature podocytes. The disease progresses to end - stage renal failure. Some affected individuals have intellectual disabilities and sensorineural hearing loss.
This process is due to mutations in the gene ARHGDIA, located in long arm of chromosome 17 (17q25.3), which encodes a protein that plays a key role in regulating signaling through Rho GTPases. The encoded protein inhibits the dissociation of the members of the Rho family of GDP (guanine diphosphate), thus keeping these factors in an inactive state. The activity of this protein is important in several cellular processes, and the expression of this gene can be altered in tumors. Through the modulation of Rho proteins, can play a role in regulating cell motility. In glioma cells, inhibits cell migration and invasion by mediating signals PLXNB3 SEMA5A and leading to inactivation of RAC1.
Mutations in the gene cause ARHGDIA type 8 nephrotic syndrome cause hyperactivation 3 Rho GTPases due to loss of function of ARHGDIA, causing alteration of cell motility. Mutations cause an imbalance in the active and inactive forms of Rho GTPases, leading to changes in the actin cytoskeleton in podocytes.
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 8 by complete PCR amplification of the exons of the gene ARHGDIA 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).