Related myopathy type VI collagen (Collagen VI related myopathy) - Genes COL6A1, COL6A2, COL6A3 and
Related myopathy VI collagen type encompasses a group of disorders that affect the skeletal muscles and connective tissue. Most affected individuals manifest muscle weakness and contractures that restrict the movement of affected joints and worsen over time. They described various forms of myopathy related to type VI collagen, which vary in intensity: Bethlem myopathy corresponding to the mildest form, moderate intermediate form and Ullrich congenital muscular dystrophy, which is the most serious.
Bethlem myopathy is a disease that mainly affects skeletal muscles. Affected individuals have progressive muscle weakness and contractures develop in your fingers, wrists, elbows and ankles that can restrict movement. In addition, some affected people have skin abnormalities as follicular hyperkeratosis. The characteristics of the Bethlem myopathy can occur at any age. Some people have symptoms of the disease even before birth. Other affected individuals develop symptoms shortly after birth, including low muscle tone and torticollis. People whose symptoms appear in childhood may have some of the delayed development milestones, such as sitting or walking. Others do not exhibit characteristics of the disease until late adulthood. Approximately two - thirds of people with Bethlem myopathy over 50 years will have to use a walker or wheelchair.
Meanwhile, the intermediate form of myopathy related to type VI collagen is characterized by muscle weakness that begins in childhood. Affected children are able to walk, but walking becomes increasingly difficult from early adulthood. These people develop in childhood contractures in the ankles, elbows, knees and spine. In some affected individuals, respiratory muscles weaken, requiring mechanical ventilation, particularly during sleep.
More severe form, known as Ullrich congenital muscular dystrophy is characterized by the manifestation of a muscle weakness that begins shortly after birth. This is often severe muscle weakness and individuals most affected are unable to walk unassisted. Affected individuals develop stiffness in the joints of your knees and elbows that can restrict movement. These people have hypermobility on her wrists and ankles. Respiratory muscles may also weaken, requiring mechanical ventilation. In addition, some people have skin abnormalities as follicular hyperkeratosis that develops around the elbows and knees.
This disease is due to mutations in the COL6A1 genes, located on the long arm of chromosome 21 (21q22.3), COL6A2, located on the long arm of chromosome 21 (21q22.3) and COL6A3, located on the long arm of chromosome 2 (2q37). Mutations in these genes may cause undesirable various forms of myopathy related to type VI collagen. Each of these genes encodes a component (?1 chain, ?2 and ?3, respectively) of a protein called collagen type VI. This protein plays an important role in muscle, particularly in skeletal muscle. VI collagen type part of the extracellular matrix surrounding cells and skeletal muscle cells that make up the connective tissue, providing strength and flexibility of structures throughout the body, including the skin and joints. The extracellular matrix is necessary for stability and cell growth.
They have identified at least 38 mutations in the COL6A1 gene. The mutations described so far in the COL6A1 gene were: missense mutations (17), and cutting mutations -splicing- joint (10), small deletions (8) and larger deletions (3). Meanwhile, they have been recognized COL6A2 66 mutations in the gene, of which: missense mutations (27), and cutting mutations -splicing- junction (21), small deletions (6), small insertions (3), deletions major (8), and complex rearrangements (1). As for the COL6A3 gene mutations they have been described 32, of which: missense mutations (20), and -splicing- mutations cutting member (8), small deletions (2), small insertions / deletions (1) and deletions greater (1). Most of these mutations change amino acids in the chain ?1, ?2 and ?3, which results in the absence or severe deficiency of collagen type VI. While it is difficult to predict what kind of mutation will lead to what form of myopathy type VI collagen related to generally lower concentrations of collagen type VI results in more severe signs and symptoms that begin earlier in life. The absence or deficiency of collagen type VI interrupts the extracellular matrix surrounding the muscle cells and connective tissue progressively decreases, leading to muscle weakness, spasms and other signs and symptoms related myopathy collagen VI.
Related myopathy VI collagen type can be inherited in an autosomal dominant pattern, which means that a copy of the altered gene in each cell is sufficient to express the alteration. Bethlem myopathy usually inherited as an autosomal dominant, as some cases of the intermediate form and a few rare cases Ullrich congenital muscular dystrophy. Most cases are due to new mutations in the gene and occur in people with no history of disease in your family. In other cases, an affected person inherits the mutation from an affected parent. Furthermore, related myopathy collagen type VI can be inherited in an autosomal recessive pattern, which means that both copies of the gene in every cell have mutations. The Ullrich congenital muscular dystrophy is usually inherited in an autosomal recessive manner, as some cases of the intermediate form and a few rare cases of Bethlem myopathy. 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 myopathy related to type VI collagen, by complete PCR amplification of the exons of the COL6A1, COL6A3 COL6A2 and genes, respectively, 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).