Instituto Valenciano de Microbiología

Masía El Romeral
Ctra. de Bétera a San Antonio Km. 0.3
46117 Bétera (Valencia)
Phone. 96 169 17 02
Fax 96 169 16 37
CIF B-96337217


Small cerebral vessels related COL4A1, disease ..., (COL4A1-related brain small-vessel disease) - Gen COL4A1            

Disease related small cerebral vessels COL4A1, is part of a group of diseases called COL4A1 related disorders. Diseases of this group have a number of signs and symptoms involving the fragility of blood vessels. In particular, the small cerebral vessels disease related COL4A1 characterized by weakened blood vessels in the brain.

Often the first sign of the condition is stroke, which usually occurs in mid-adulthood. In affected individuals, stroke is usually a hemorrhagic stroke, ischemic stroke but may also occur. People with this condition have an increased risk of having more than one stroke in his life. Affected individuals also have leukoencephalopathy and may have migraines and headaches accompanied by auras.

Some people have an eye abnormality called Axenfeld-Rieger Anomaly, involving underdevelopment and eventual rupture of the iris and a pupil which is not centered. Other eye problems may include cataract and retinal arterial tortuosity. The Axenfeld-Rieger anomaly and cataracts can cause vision problems. Arterial tortuosity of the retina can lead to bleeding inside the eye after any minor trauma, leading to temporary loss of vision. The severity of the disease varies greatly among affected individuals. Some people do not show signs or symptoms of the disease.

This process is due to alterations in gene sequence COL4A1 (collagen type IV alpha 1), located on the long arm of chromosome 13 (13q34) encoding the alpha1 chain of collagen type IV. This chain is combined with other chain alpha 1 and alpha 2 chain to a complete molecule. The type IV collagen molecules are joined together to form complex networks of proteins. These networks proteins are the major component of basement membranes. The alpha 1-1-2 type IV collagen network plays an important role in basement membranes of virtually all tissues of the body, especially in the basement membranes of blood vessels. The network makes collagen type IV basement membranes interact with nearby cells, play a role in migration, growth, proliferation, differentiation and cell survival.

Most of the identified mutations responsible for disease COL4A1 small cerebral vessels related COL4A1 gene , consisting of amino acid changes in the alpha chain of type IV collagen 1. Specifically, mutations replacing the amino acid glycine by a different one of several places in this collagen chain amino acid. Substitution of another amino acid for glycine in alpha1 chain prevents this chain can bind to other strings to form a complete molecule type IV collagen. This alteration in collagen type IV inhibits the formation of protein networks and the correct development of basement membranes, which causes the tissues to weaken. As a result, blood vessels throughout the body become brittle, leading to the signs and symptoms of this disease. It is unclear how mutations in the COL4A1 gene can lead to different conditions. It is likely that mutations in different regions of this gene have a role in the development of the various signs and symptoms of disorders related to COL4A1. Other genetic changes and environmental factors may also contribute to the characteristics of different disorders related to COL4A1.

This process is inherited as an autosomal dominant, which means that a copy of the altered gene in each cell is sufficient to express the disease. In most cases, an affected person has an affected parent. Rarely, the disease is due to new mutations in the gene that occur in people with no history of disease in your family.

Tests in IVAMI: in IVAMI perform detection of mutations associated with disease related small cerebral vessels with COL4A1, by complete PCR amplification of exons COL4A1 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).