Congenital nephrotic syndrome ... (Congenital nephrotic syndrome) - Genes NPHS1 and NPHS2
Congenital nephrotic syndrome is a kidney disease that begins in childhood and typically causes irreversible renal failure in early childhood. Children with congenital nephrotic syndrome begin to show symptoms of the disease between birth and 3 months.
The characteristics of congenital nephrotic syndrome are due to failure of the kidneys to filter waste products from the blood and remove them in the urine. Signs and symptoms of this disease include proteinuria, hypercholesterolemia, ascites and edema. Affected individuals may also have hematuria, which can lead to anemia, abnormal blood clots or leucopenia. Leukopenia can cause a weakened immune system and frequent infections in people with congenital nephrotic syndrome. Children with congenital nephrotic syndrome often develop ESRD between 2 and 8 years old, but with treatment, some may not have kidney failure until adolescence or early adulthood.
In most cases, this process is due to mutations in the NPHS1 gene (NPHS1, nephrin), located on the long arm of chromosome 19 (19q13.1) or NPHS2 gene (NPHS2, podocin), located in the long arm of chromosome 1 (1q25.2). These genes encode proteins found in the kidneys. Specifically, the proteins encoded from genes NPHS1 and NPHS2 (nephrin and podocin, respectively) are mainly located in the kidneys. Specifically, both proteins are found in podocytes, which are located in the glomeruli. Nephrin and podocin found on the cell surface in the slit diaphragm. The slit diaphragm is known as a filtration barrier as it captures blood proteins so that they remain in the body while allowing other molecules such as sugars and salts are excreted in the urine. Proteins are also involved in cell signaling podocytes, helping the cell to adapt to the changes that occur during the filtration process.
They have been described at least 250 mutations in the NPHS1 gene in people with congenital nephrotic syndrome. NPHS 1 gene mutations have been identified in all cases of congenital nephrotic syndrome of the Finnish type. This form of the disease found in people of Finnish descent. Two specific mutations, which result in the synthesis of an abnormally short, nonfunctional protein nephrin represent almost all cases. The first mutation, known as Finnmajor, L41fsX90, is responsible for 78 percent of cases. The second mutation, known as Finnminor, R1109X, is responsible for 16 percent of cases. NPHS1 gene mutations may also be responsible for congenital nephrotic syndrome in no Finnish subjects. Most of these mutations result in the synthesis of an abnormal protein nephrin it is retained within the cell and can not reach the surface of the podocytes. A deficiency of functional cell surface nephrin in podocytes alters forming slit diaphragms normal. Without a functional slot diaphragm, molecules pass through the kidneys abnormally and excreted in urine. The filtering capacity of the kidneys deteriorates from birth, eventually leading to end - stage kidney disease.
Meanwhile, they have identified at least 170 mutations in the gene NPHS2 in people with congenital nephrotic syndrome. Mutations in this gene appear to be the most common cause of congenital nephrotic syndrome. Most NPHS2 gene mutations in amino acid changes consist podocin protein. These mutations result in a reduction or absence of functional protein, disrupting the formation of diaphragms normal slit. Without a slit diaphragm functional molecules pass through the kidneys abnormally and excreted in the urine. The filtering capacity of the kidneys deteriorates from birth, eventually leading to end - stage kidney disease.
Mutations in other genes are responsible for a small number of cases of congenital nephrotic syndrome. 15 to 20 percent of individuals with congenital nephrotic syndrome have an identified one of the genes associated with this process mutation. In these cases, the reason for the development of this process can be the environment, including infections such as syphilis or toxoplasmosis, or can be caused by mutations in genes unidentified.
This disease is inherited in an autosomal recessive pattern, which means that 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 congenital nephrotic syndrome by complete PCR amplification of exons and NPHS2 NPHS1 genes, 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).