Nephrotic type 3 syndrome - PLCE1 gene

Nephrotic syndrome type 3 is a disease that causes kidney malfunction glomerular filter clinically characterized by proteinuria, edema, and renal disease (ESRD).

Signs and symptoms of the disease include diffuse mesangial sclerosis, focal segmental glomerulosclerosis. Some affected individuals have inherited steroid resistant form.

This process is due to mutations in the gene PLCE1, located on the short arm of chromosome 10 (10q23) encoding phospholipase C epsilon which catalyzes the hydrolysis of phosphatidylinositol-4,5-bisphosphate to produce two secondary messengers inositol 1, 4,5-triphosphate (IP3) and diacylglycerol (DAG). These second messengers then regulate diverse cellular processes that affect the growth, differentiation, and gene expression. This enzyme is regulated by small GTPases of the Ras and Rho family and heterotrimeric G proteins. In addition to its catalytic activity, phospholipase C is an N-terminal which acts as a guanine nucleotide exchange (GEF) domain.

In mutations PLCE1 gene, it was found to have an expression of 10 to 11 times greater in glomeruli compared to bark or renal medulla, and approximately an expression 6 times higher in podocytes containing glomeruli compared to glomeruli with little podocytes. Other mutations in the gene interfere with repair mechanisms glomerulus.

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 3 by the complete PCR amplification of exons PLCE1 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).