Fibronectin glomerulopathy (Fibronectin glomerulopathy) - Gen FN1.
The fibronectin glomerulopathy is a kidney disease that usually develops between early and middle adulthood, but can occur at any age. Eventually, fibronectin glomerulopathy leads to end stage renal disease.
Signs and symptoms associated with the disease can include hematuria and proteinuria, hypertension and renal tubular acidosis. The kidneys of affected individuals have large deposits of fibronectin-1 protein in glomeruli. Deposits fibronectin-1 affect the filterability of the glomeruli. Approximately 15 to 20 years after the onset of signs and symptoms, affected individuals often develop ESRD. People affected can be treated by a kidney transplant but in some cases, the disease recurs after transplantation.
It is estimated that mutations in the FN1 gene are responsible for 40% of cases of fibronectin glomerulopathy. The cause of the remaining cases is unknown. The FN1 gene, located on the long arm of chromosome 2 (2q34) encodes two types of fibronectin-1 protein: soluble plasma fibronectin-1 and fibronectin-1 insoluble cell. Liver cells produce soluble fibronectin-1 plasma and released into the bloodstream, where mainly involved in blood clotting and wound healing. The soluble plasma type fulfills its function in the extracellular spaces, joining and other cell surface proteins, including other fibronectin-1 proteins. The binding of these proteins form fibers that help tissue repair after injury. Fibronectin-1 binding also helps with continuous formation of the extracellular matrix. This matrix provides structure and strength to the tissues that support organs. Many other types of cells produce insoluble fibronectin-1 cell, which is released into the extracellular space and contributes to the creation of fibers and extracellular matrix. Both types of fibronectin-1 help cells to expand and migrate to cover more space and also influence the shape and cell differentiation.
They have been described at least three mutations in the FN1 gene in individuals with fibronectin glomerulopathy. The identified mutations change amino acids in fibronectin-1 protein. A mutation that occurs in multiple families replaces the amino acid tyrosine by the amino acid cysteine at position 973 of the fibronectin-1 protein (Tyr973Cys or Y973C). FN1 gene mutations impair the ability of the protein to bind to cells and proteins. Fibronectin-1 unbound protein, specifically fibronectin-1 soluble plasma, is deposited in the renal glomeruli. These structures are groups of small blood vessels in the kidneys that filter waste products from the blood, which is then released into the urine. Although there is an abundance of fibronectin-1 in glomeruli, the extracellular matrix that supports blood vessels is weak because the fibronectin-1 altered can not help in the continuous matrix formation. Without a cellular network support, the glomeruli are less able to filter waste. As a result, products that are normally retained by the body, such as blood proteins and are released through urine. Eventually, the kidneys ' ability to filter waste decreases until the kidneys can not function, leading to end stage renal disease.
When fibronectin glomerulopathy is due to mutations in the FN1 gene is inherited in an autosomal dominant pattern, which means that a copy of the altered gene in each cell is sufficient to express the disease. In some of these cases, an affected person inherits the mutation from an affected parent. Other cases are due to new mutations in the gene and occur in people with no history of disease in your family. Some people who have altered the FN1 gene never develop the disease, a situation known as reduced penetrance.
Tests in IVAMI: in IVAMI perform detection of mutations associated with fibronectin glomerulopathy, by complete PCR amplification of the exons of the FN1 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).