MYH7

The MYH7 gene provides instructions for making a protein known as the cardiac beta (β)-myosin heavy chain. This protein is found in heart (cardiac) muscle and in type I skeletal muscle fibers. Type I fibers, which are also known as slow-twitch fibers, are one of two types of fibers that make up skeletal muscles. Type I fibers are the primary component of skeletal muscles that are resistant to fatigue. For example, muscles involved in posture, such as the neck muscles that hold the head steady, are made predominantly of type I fibers.

In cardiac and skeletal muscle cells, the β-myosin heavy chain forms part of a larger protein called type II myosin. This type of myosin generates the mechanical force that is needed for muscles to contract. In the heart, regular contractions of cardiac muscle pump blood to the rest of the body. The coordinated contraction and relaxation of skeletal muscles allow the body to move.

Each type II myosin protein consists of two heavy chains (produced from the MYH7 gene) and two pairs of regulatory light chains (produced from several other genes). The heavy chains each have two parts: a head region and a tail region. The head region interacts with actin, a protein that is important for cell movement and shape. The long tail region interacts with other proteins, including the tail regions of other myosin proteins.

Laing distal myopathy - caused by mutations in the MYH7 gene

At least five mutations in the MYH7 gene have been found to cause Laing distal myopathy. These genetic changes occur in the tail region of the β-myosin heavy chain. Some of these mutations change single protein building blocks (amino acids), while others delete a single amino acid from the heavy chain. Changes in the MYH7 gene probably disrupt the normal function of type II myosin in muscle cells. Specifically, researchers suspect that mutations alter the structure of the tail region of the β-myosin heavy chain. The altered tail region may be unable to interact with other proteins, including the tail regions of other myosin proteins. It is unclear how these changes in the structure and function of myosin lead to progressive muscle weakness in people with Laing distal myopathy.

other disorders - caused by mutations in the MYH7 gene

Mutations in the MYH7 gene cause several other disorders of cardiac and skeletal muscle. Two of these disorders, familial hypertrophic cardiomyopathy type 1 and dilated cardiomyopathy type 1S, primarily affect cardiac muscle. Hypertrophic cardiomyopathy is a thickening of the cardiac muscle that forces the heart to work harder to pump blood. This condition is often associated with an abnormal heartbeat (arrhythmia) and can lead to heart failure and sudden death. Dilated cardiomyopathy is a condition that weakens and enlarges the heart, preventing it from pumping blood efficiently. Dilated cardiomyopathy also increases the risk of heart failure and premature death. Researchers have found more than 200 MYH7 mutations in people with familial hypertrophic cardiomyopathy type 1 and about a dozen mutations in people with dilated cardiomyopathy type 1S.

MYH7 mutations are also responsible for a skeletal muscle disorder called myosin storage myopathy (also known as hyaline body myopathy). This condition causes muscle weakness that does not worsen over time or worsens very slowly. Affected individuals may have a waddling gait, trouble climbing stairs, and difficulty lifting the arms above shoulder level. Myosin storage myopathy is characterized by the formation of clumps called hyaline bodies, which include type II myosin protein, within type I skeletal muscle fibers. It is unclear why these clumps form and what effect they have on skeletal muscle function. At least four MYH7 mutations associated with myosin storage myopathy have been identified.

The MYH7 mutations responsible for these disorders of cardiac and skeletal muscle likely disrupt the normal structure and function of type II myosin. Little is known about the connection between abnormal myosin and the particular signs and symptoms of each disorder. Researchers are working to determine why some of the conditions that result from MYH7 mutations predominantly affect cardiac muscle and others predominantly affect skeletal muscle.