Alport syndrome ... (Alport syndrome) - Genes COL4A3, COL4A4, COL4A5 and.
Alport syndrome is a progressive disease of genetic origin characterized by persistent hematuria that eventually progresses to ESRD. Often Alport syndrome is associated with progressive sensorineural hearing loss (caused by abnormalities of the inner ear and sensorineural hearing loss) and eye injuries, which rarely lead to loss of vision. Other signs and symptoms may include additional with hematuria, proteinuria and discoloration of the retina. Significant hearing loss, eye abnormalities and progressive kidney disease are more common in men with Alport syndrome than women affected.
The causes leading syndrome Alport are defects in the chains ?3, ?4 ?5 or that generate molecules combined type IV collagen. The type IV collagen molecules are connected together to form complex networks of proteins that constitute a large part of basement membranes, especially those of the kidney, eye and inner ear.
COL4A3 genes located on the long arm of chromosome 2 (2q36-P37), COL4A4, located on the long arm of chromosome 2 (2q35-p37) and COL4A5, located on the long arm of chromosome X (Xq22), encoding chains ?3, ?4 ?5 or type IV collagen. This protein plays an essential role in renal glomeruli. Genetic alterations localized in the COL4A3, COL4A4 and COL4A5 genes lead to abnormalities in type IV collagen, common in the glomeruli, which prevents the kidneys adequately filter blood plasma, ultimately causing the own kidney failure people with Alport syndrome . Collagen type IV is also a major component of the structures of the inner ear, particularly the organ of Corti, responsible for transforming the sound waves into nerve impulses to the brain. Therefore, when it is altered can lead to hearing loss.
Until now, they have been located throughout the coding sequence of COL4A5 gene, more than 400 mutations associated with Alport syndrome. Many of these mutations cause altered region of the ?5 chains combine with the other chains of type IV collagen, structurally altering or truncating molecules collagen type IV. Other alterations simply reduce or prevent the production of ?5 chains. Following these cases, a severe deficiency of collagen type IV, as we have seen, particularly affecting kidney basement membranes, inner ear and eyes occurs. The same goes for the ?3 and ?4 chains encoded by the COL4A3 and COL4A4 genes, which have been described mutations 40 and 20, respectively.
Alport syndrome can have different inheritance patterns. About 80% of cases are X - linked, as are due to mutations in COL4A5 gene , . In males, who have only one X chromosome, an altered copy of COL4A5 gene is sufficient to generate kidney failure and other serious own disease symptoms. In women, who have two X chromosomes, a mutation in the COL4A5 gene copy generally only results in hematuria, although some women experience more severe symptoms. In approximately 15% of cases, Alport syndrome is the result of mutations in both copies of the COL4A3 or COL4A4 gene is inherited in an autosomal recessive pattern, which means that both copies of the gene in every cell must have mutations so that the 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. Carriers of these cases may be affected, sometimes a less serious condition Alport syndrome, called Thin Basement Membrane Nephropathy (NMBD), characterized by hematuria. 5% in other cases, Alport syndrome has an autosomal dominant inheritance due to mutations in COL4A3 or COL4A4. Not yet been elucidated why individuals heterozygous for mutations in COL4A3 or COL4A4 genes may present Alport syndrome or NMBD.
Tests in IVAMI: in IVAMI perform detection of mutations associated with Alport syndrome by complete PCR amplification of exons of COL4A3, COL4A5 COL4A4 and genes, respectively, and subsequent sequencing. It is recommended to start the study based on family history of each patient. If lack or absence of a family history suggested by the COL4A5 gene start, associated with the sex - linked form of the disease, and its alteration is responsible for 80% of cases of Alport syndrome of.
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).