Lowe syndrome ... (Lowe syndrome) - Gen OCRL.
Lowe syndrome is a disorder that primarily affects the eyes, brain and kidneys and which occurs almost exclusively in males.
Signs and symptoms of the disease include congenital cataracts and other eye abnormalities that can affect vision, developmental delay and intellectual capacity, behavioral problems, seizures, neonatal hypotonia which can contribute to feeding difficulties, respiratory problems, and delayed in the development of motor skills. Additionally, there may be Renal abnormalities may lead to an alteration known as renal Fanconi syndrome, in which the kidneys are unable to absorb important nutrients in the bloodstream. These kidney problems cause increased urination, dehydration and metabolic acidosis, and can cause hypophosphatemic rickets. Moreover, progressive kidney disease in older children and adults with Lowe syndrome can cause kidney failure end - stage kidney (ESRD). About half of affected infants develop an infantile glaucoma, characterized by increased intraocular pressure.
This process is due to mutations in the gene OCRL, located on the long arm of chromosome X (Xq25). This gene encodes an enzyme that helps to modify fat molecules called membrane phospholipids. By controlling the concentrations of membrane phospholipids, the enzyme OCRL helps regulate the transport of certain substances to and from the cell membrane. This enzyme is also involved in the regulation of the actin cytoskeleton, which has several critical functions, including the determination of cell shape and cell movement. Recent research suggests that OCRL enzyme may also play a role in the formation, function, and maintenance of cilia.
They have identified more than 120 mutations in the gene OCRL people with Lowe syndrome. Some mutations in the gene encoding avoid any enzyme OCRL. Other mutations reduce or eliminate the activity of the enzyme or prevent interaction with other proteins within the cell. Work is being done to determine how mutations in the gene OCRL give rise to the characteristic features of Lowe syndrome. Because the OCRL enzyme is present throughout the body, it is unclear why the medical problems associated with this disorder are mostly limited to the brain, kidneys and eyes. Other enzymes may be able to compensate for the defective enzyme in unaffected tissues.
This disease is inherited in an X - linked pattern in males, an altered copy of the gene in each cell is sufficient to cause alteration. In women, a mutation must be present in both copies of the gene to cause the disease. Most X - linked disorders affect males much more frequently than women. A feature of the X - linked inheritance is that fathers can not pass X - linked traits to their sons chromosome. In some cases of Lowe syndrome, an affected male inherits the mutation of a mother carrying an altered copy of the gene OCRL. Other cases are caused by new mutations in the gene and occur in men with no history of disease in your family. Women who carry a mutated copy of the gene do not have the characteristic features of Lowe syndrome. However, most female carriers have changes in the lens of the eye that can be observed with a thorough eye exam. These changes usually do not affect vision.
Tests in IVAMI: in IVAMI perform detection of mutations associated with Lowe syndrome by complete PCR amplification of exons OCRL 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).