Hereditary myopathy with early respiratory failure (HMERF) - TTN gene
Hereditary myopathy with early respiratory failure (HMERF) is a hereditary muscular disease that predominantly affects the proximal muscles and muscles that are needed to breathe.
The main signs and symptoms of HMERF usually appear in adulthood, on average, around 35 years of age. The first affected muscles in HMERF are the neck flexors. Other proximal muscles that become weak in people with HMERF include the muscles of the hips, thighs and arms. Some affected individuals also have weakness in the muscles of the leg and in the dorsal extensors of the foot. This disease also causes intense weakness in the thorax muscles involved in breathing, particularly the diaphragm. This weakness leads to respiratory problems and respiratory failure that can be potentially fatal.
This process is usually due to mutations in the TTN (titin) gene, located on the long arm of chromosome 2 (2q31.2); however, in rare cases, people with the characteristics of HMERF do not have mutations identified in this gene and the cause of the disease in these cases is unknown. This gene encodes a protein called titin, which is found in the sarcomeres of many types of muscle cells, including cardiomyocytes. This protein has several functions within the sarcomeres. One of its most important tasks is to provide structure, flexibility and stability to these cellular structures. In addition, it also plays a role in chemical signaling and in the assembly of new sarcomeres.
Several mutations in the TTN gene have been identified in people with hereditary myopathy with early respiratory failure (HMERF). The described mutations give rise to the synthesis of an altered version of the titin protein that cannot be folded into its normal three-dimensional shape. Although work is being done to determine how abnormally bent titin contributes to muscle damage and the signs and symptoms of HMERF, it is not clear why these effects are generally limited to certain skeletal muscles and respiratory muscles.
This disease is 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.
Tests performed in IVAMI: in IVAMI we perform the detection of mutations associated with hereditary myopathy with early respiratory failure (HMERF), by complete PCR amplification of the exons of the TTN gene, and their subsequent sequencing.
Recommended samples: blood drawn with EDTA for separation of blood leukocytes, or card impregnated with dried blood sample (IVAMI can mail the card to deposit the blood sample).