Glomerulopathy C3 (C3 glomerulopathy) - Genes ADAM19, C3, C3AR1, C8A, CD46, CFB, CFD, CFH, CFHR1, CFHR2, CFHR3, CFHR5, IFC and CR1
The C3 glomerulopathy (C3G) is a group of related diseases that cause renal malfunction. The main features of the C3 glomerulopathy include proteinuria, hematuria, small amounts of urine, low protein concentrations in the blood, and swelling in many areas of the body. In addition, affected individuals may have particularly low concentrations of the protein in blood C3. Kidney problems associated with C3 glomerulopathy tend to worsen over time. About half of affected individuals develop end - stage renal disease (ESRD) approximately 10 years after diagnosis. ESRD is a potentially fatal condition that prevents the kidneys filter liquids and remove waste products from the body effectively.
They described two main forms glomerulopathy C3: dense deposit disease and glomerulonephritis C3. Although the two diseases have similar kidney problems, the characteristics of dense deposit disease tend to appear before the C3 glomerulonephritis, usually in adolescence. However, the signs and symptoms of both diseases may not appear until adulthood.
One of the two forms of glomerulopathy C3, dense deposit disease, may also be associated with other non-renal function disorders. For example, people with dense deposit disease may develop partial lipodystrophy, a process characterized by a deficiency in fatty tissue under the skin at the top of the body. In addition, some people with dense deposit disease develop an accumulation of yellow deposits, called drusen in the retina. These deposits usually appear in childhood or adolescence and can cause vision problems in the future.
The C3 glomerulopathy is associated with changes in many genes. These genes include:
- ADAM19 (ADAM metallopeptidase domain 19, 5q33.3).
- C3 (complement component 3, 19p13.3-p13.2).
- C3AR1 (complement component receptor 1 on the 3rd, 12p13.31).
- C8A (complement component alpha subunit 8, 1p32).
- CD46 (CD46 molecule, 1q32).
- CFB (complement factor B, 6p21.3).
- CFD (complement factor D, 19p13.3).
- CFH (complement factor H, 1q32).
- CFHR1 (complement factor H related 1, 1q32).
- CFHR2 (complement factor H related 2, 1q31.3).
- CFHR3 (complement factor H related 3, 1q32).
- CFHR5 (complement factor H related 5, 1q31.3).
- CFI (complement factor I, 4q25).
- CR1 (complement component 3b / 4b receptor 1 (Knops blood group), 1q32).
Most of these genes encode protein synthesis that help regulate a part of the innate immune response in the body called the complement system. This system is a group of proteins that act together to destroy foreign invaders, such as bacteria and viruses, trigger inflammation, and remove waste from cells and tissues. The complement system must be carefully regulated so that targets only unwanted and does not damage healthy cells of the body elements. A specific mutation in one of the related genes complement system, the CFHR5 gene (complement factor H related 5), has been identified in people with glomerulopathy C3 Mediterranean Cyprus. Mutations in the CFH gene (complement factor H) and C3 (complement component 3), and other related genes complement system have been described as determining the development of glomerulopathy C3 in other populations. Known mutations represent only a small percentage of all cases. In most cases, the cause of the disease is unknown.
Several polymorphisms in genes associated with the complement system genes are associated with increased likelihood of developing glomerulopathy C3. In some cases, the increased risk is associated with a group of specific variants in several genes, a situation known as risk haplotype C3 glomerulopathy. While these polymorphisms increase the risk of C3 glomerulopathy, many people who inherit these genetic changes never develop the disease. Genetic changes associated with the disease increases activation of the complement system. Hyperactive system damages the glomeruli in the kidneys. Damage to the glomerulus prevents the kidneys filter waste products efficiently and can lead to end stage renal disease. It is believed that uncontrolled activation of the complement system is also responsible for other health problems that may occur in dense deposit disease, including acquired partial lipodystrophy and accumulation of drusen in the retina. Work is underway to determine how these health problems are related to overactivity of the complement system. Moreover, the glomerulopathy C3 may also derive from the presence of autoantibodies. Autoantibodies lead to the development of the disease by altering the activity of proteins involved in the regulation of the complement system.
Most cases are sporadic C3 glomerulopathy, meaning that occur in people with no history of disease in your family. They have identified only a few families with more than one family member with C3 glomerulopathy. However, many people affected have had close relatives with autoimmune diseases. The relationship between glomerulopathy C3 and autoimmune diseases is not fully understood.
Tests performed in IVAMI: in IVAMI perform the detection of mutations associated with glomerulopathy C3 through the complete PCR amplification of the exons of ADAM19, C3, C3AR1, C8A, CD46, CFB, CFD, CFH, CFHR1, CFHR2 genes, CFHR3, CFHR5, IFC and CR1, respectively, 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).