Laing distal myopathy (Laing distal myopathy) - Gen MYH7
Laing distal myopathy The is a disease that affects skeletal muscles and is characterized by an early and selective weakness toe and ankle dorsiflexors. This disease causes progressive weakness that manifests in childhood. The disease initially affects dorsiflexors ankle and big toe and then the finger extensors, especially the third and fourth finger. All patients have early weakness in neck flexion. In addition to muscle weakness in the hands and feet, the disease causes weakness in various muscles of the neck and face. A decade or more after the onset of symptoms, weakness also extends to the muscles of the legs, hips and shoulders. The distal myopathy Laing progresses very gradually, and most people affected preserve mobility throughout life. Life expectancy is normal in those affected.
This process is due to mutations in MYH7 (myosin heavy chain 7), located on the long arm of chromosome 14 (14q11.2). This gene encodes a protein called myosin beta (?) cardiac heavy chain. This protein is found in the heart muscle and skeletal muscle fibers of type I cells cardiac and skeletal muscle, the form of ? myosin heavy chain part of a larger protein called myosin type II. Each protein myosin type II consists of two heavy chains (encoded from MYH7) and two pairs of regulatory light chain (encoded from other genes). Heavy chains have two parts: a head region and tail region. The head region, called the motor domain interacts with a protein called actin thin filament. The region long tail interacts with other proteins, including the regions of other tail proteins myosin. Type II myosin generates mechanical force needed for muscles to contract and is an integral part of the sarcomeres.
They have identified at least five mutations MYH7 leading to the distal myopathy Laing. Most of these mutations result in changes in the tail region of the heavy chain of myosin ?. Some of these mutations change the individual amino acids, while others remove a single amino acid of the heavy chain. Changes in MYH7 probably alter the normal function of myosin type II muscle cells. Specifically, it is believed that mutations alter the structure of the tail region of the heavy chain of myosin ?. The region of altered tail may be unable to interact with other proteins, including the tail regions of other proteins myosin. It is unclear how these changes in the structure and function of myosin leading to progressive muscle weakness in people with the disease.
Laing distal myopathy the inherited in an autosomal dominant pattern, which means that a copy of the altered gene in each cell is sufficient for the disease to be expressed. In most cases, an affected person inherits the mutation from an affected parent. A small percentage of cases are due to new mutations in the gene. These cases occur in people with no history of disease in your family.
Tests in IVAMI: in IVAMI perform detection of mutations associated with distal myopathy Laing, by complete PCR amplification of exons MYH7, 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).