Neuropathy Hereditary distal motor type II (Distal hereditary neuropathy engine type II) - Genes HSPB1 and HSPB8.
Distal hereditary motor neuropathy type II is a progressive disease that affects the nerve cells of the spinal cord, leading to muscle weakness and impaired movement, primarily in the legs. This disease manifests from adolescence to middle adulthood. Initial symptoms include cramps or weakness in the muscles of the big toe , and later around the foot. Over a period of about 5 to 10 years, infected people have atrophy in the lower extremities. As a result, they have trouble walking and running and, over time, can manifest complete paralysis of the legs. Thigh muscles may also be affected, although this usually occurs later and is less severe. Some affected individuals have weakened muscles of the hands and forearms. This weakening is less pronounced than in the lower limbs and usually does not lead to paralysis.
This process is due to mutations in genes HSPB1, located on the long arm of chromosome 7 (7q11.23) and HSPB8, located on the long arm of chromosome 12 (12q24.23). These genes encode heat shock proteins termed beta-1 and beta-8. The heat shock proteins help protect cells under adverse conditions such as infection, inflammation, exposure to toxins, the high temperature, injury and disease and block signals leading to apoptosis. Also seem to be involved in activities such as cell movement, stabilizing the cytoskeleton, the folding and stabilization of newly encoded proteins, and repair of damaged proteins. These proteins also appear to play a role in muscle contraction. The heat shock protein beta-1 and beta 8 are in cells throughout the body and are abundant in nerve cells. In nerve cells the heat shock protein beta-1 helps organize neurofilament maintaining the diameter of the axons. Maintaining proper axon diameter is essential for the efficient transmission of nerve impulses. The function of heat shock protein beta-8 is not well understood, but has been shown to interact with the heat shock protein beta-1.
They have identified at least six mutations in the gene HSPB1, and 2 mutations in the gene HSPB8 in people with distal motor neuropathy hereditary type II. The HSPB1 and HSPB8 genetic mutation changes the amino acid sequence of the protein. If any of the altered proteins can be more prone to aggregate and form lumps. Aggregates of heat shock proteins may block transport of substances essential for the proper functioning of nerve axons. Disruption of other cellular functions in which these proteins are involved may also contribute to the signs and symptoms of distal hereditary motor neuropathy type II.
Motor neuropathy distal hereditary type II is inherited in an autosomal dominant, which means that a copy of the altered gene in each cell is sufficient for the disease to be expressed.
Tests in IVAMI: in IVAMI perform detection of mutations associated with hereditary neuropathy distal motor type II, by complete PCR amplification of the exons of HSPB1 and HSPB8, respectively, and subsequent sequencing genes.
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).