Retinal blood macroaneurysm with supravalvular pulmonary stenosis (arterial Retinal macroaneurysm With supravalvular pulmonic stenosis -RAMSVPS-) - Gen IGFBP7.

Retinal arterial supravalvar macroaneurysm with pulmonary stenosis (RAMSVPS) is a disorder that affects the blood vessels of the eyes and the heart and usually manifests in infancy or childhood. This disease damages arteries in the retina, gradually develop multiple small protrusions. Finally, macroaneurysms that occur rupture, resulting in bleeding that can spread to other areas of the eyes and cause vision loss.

At the same time, people with RAMSVPS also have supravalvar pulmonary stenosis, which affects the circulation between the heart and lungs. Supravalvular pulmonary stenosis affects the blood flow to the lungs, where the blood is oxygenated to carry oxygen to the tissues throughout the body cells. As a result, less oxygen is transported through the bloodstream, resulting in signs and symptoms include shortness of breath, rapid heartbeat, fatigue, and swelling in the face, foot, or abdomen.

This process is due to mutations in the gene IGFBP7, located on the long arm of chromosome 4 (4q12). This gene encodes a protein called protein factor binding insulin - like 7 (IGFBP7) growth. Factors like growth (IGF) are molecules involved in growth and cell division, as well as prevention of early apoptosis. The IGFBP7 protein belongs to a group of proteins that help control the availability of IGF in fluids and tissues and increase or decrease the IGF binding to other molecules. Binding of IGFs and their receptors activate cellular signaling processes in which they are involved. The IGFBP7 protein is active in the vascular endothelium. It is believed that their interactions with IGFs and their receptors contribute to stop the BRAF signaling pathway, involved in directing cell growth.

The gene mutation responsible for RAMSVPS IGFBP7 results in an abnormally short protein IGFBP7 malfunctioning. Without protein IGFBP7 work properly to control BRAF signaling, this signaling is increased. Although it is unclear how this increase is related to the specific abnormalities of blood vessels that occur in RAMSVPS or why these anomalies are limited to the eyes and the pulmonary artery, it is likely that differences in normal concentrations of protein IGFBP7 in various parts of the body, or the presence of other proteins with similar function in different tissues can give an explanation of specific signs and symptoms of retinal blood macroaneurysm with supravalvular pulmonary stenosis.

This disease 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 retinal arterial macroaneurysm with supravalvular pulmonary stenosis (RAMSVPS), by complete PCR amplification of the exons of the gene IGFBP7, 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).