Donnai-Barrow syndrome ... (Donnai-Barrow syndrome) - Gen LRP2.
The Donnai-Barrow syndrome is a hereditary disorder that affects many parts of the body. This alteration is characterized by unusual facial features, including prominent eyes, wide apart with exterior angles directed downward, a short nose bulbous with flat nasal bridge, ears rotated back and hairline V - shaped in the center front.
People with Donnai-Barrow syndrome have sensorineural hearing loss. Often they suffer from vision problems, including deep myopia, detachment or deterioration of the retina, and progressive loss of vision. Some affected individuals have iris coloboma. In most people with this syndrome, the tissue that connects the left and right halves of the brain it is absent or underdeveloped. Affected individuals may also have other structural brain abnormalities. They generally have mild to moderate mental retardation and developmental delay. People with this syndrome may also have a congenital diaphragmatic hernia. This potentially serious birth defect allows the stomach and intestines move into the chest, displacing turn, the heart and lungs. Sometimes, people with Donnai-Barrow syndrome have abnormalities of the intestine, heart or other organs.
Donnai syndrome-Barrow, occurs as a result of mutations in the gene LRP2, located on the long arm of chromosome 2 (2q31.1). This gene encodes a protein called megalin, which acts as a receiver. Receptor proteins have specific locations proteins which act as ligands bind. When they inteaccionan both trigger signals that affect cell development and function. Megalin protein has many ligands involved in various processes in the body, including absorption of vitamins A and D, the immune function, stress response, and transport of fats in the bloodstream.
They have identified at least 12 genetic mutations in the gene LRP2 in people with Donnai-Barrow syndrome. These mutations cause absence of a functional protein megalin. The absence of functional megalin in renal tubules causes various megalin ligands are excreted in the urine instead of being absorbed into the bloodstream. The features of Donnai-Barrow syndrome are likely caused by the inability of megalin to help absorb these ligands, disruption of biochemical signaling pathways, or other effects of megalin protein nonfunctional. However, it is unclear how these alterations cause specific signs and symptoms of the disease.
Certain polymorphisms in gene LRP2 may be associated with different progression, recurrence and severity of prostate cancer in affected males. Androgens are among the ligands of megalin. A recent study suggests that prostate tumor cells can produce greater amounts of mesalamine, and therefore absorb more androgens. LRP2 gene polymorphisms that increase the activity of megalin can cause a more aggressive tumor growth, while polymorphisms that decrease the activity of megalin can reduce tumor growth.
This syndrome is inherited in an autosomal recessive pattern, that is, 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 syndrome Donnai-Barrow, by complete PCR amplification of the exons of the gene LRP2, 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).