Distal motor neuropathy type V (Distal hereditary neuropathy type engine V) - Genes BSCL2 and GARS.
Motor neuropathy distal type V is a progressive disease that affects the nerve cells of the spinal cord. This disease leads to muscle weakness and affects the movement of the hands and feet.
Symptoms of distal motor neuropathy type V usually begin during adolescence, but the appearance may vary from infancy to mid 30s. The initial symptom is usually hand cramps caused by exposure to low temperatures. The characteristic features of the disease are muscle atrophy hand (specifically on the side of the thumb and index finger and palm at the base of the thumb) and abnormalities of the foot, forming an arch. Some affected individuals eventually develop problems walking. Affected individuals have a normal life expectancy.
This process is due to mutations in genes BSCL2 and GARS.
The BSCL2 gene, located on the arm of chromosome 11 (11q13), encodes a protein called seipina, whose function is unknown. Within cells, the protein is found in the endoplasmic reticulum membrane. The endoplasmic reticulum and modifies the newly encoded transport aid of proteins, fats and other molecules to specific sites either inside or outside the cell proteins. The BSCL2 gene is active in cells throughout the body, particularly in motor neurons and in brain cells. It is believed that seipina can play a critical role in the early development of these cells. They have identified at least two mutations in the gene BSCL2 in people with type motor neuropathy distal V. These mutations change individual amino acids in the coding seipina. In mutation, the amino acid serine is replaced with the amino acid leucine at position 90 (Ser90Leu or S90L). The other mutation is the N88S mutation. Although it is unclear how these mutations result in disease, probably they alter the structure of seipina, causing them to fold in a form of three dimensional incorrect. As a result, seipina misfolded proteins accumulate in the endoplasmic reticulum. This buildup leads to damage and destroy motor neurons, leading to muscle weakness.
The GARS gene, located on the short arm of chromosome 7 (7p15), encodes an enzyme called glycyl-tRNA synthetase. This enzyme is found in all cell types and play an important role in protein synthesis. During protein synthesis, amino acids are linked together in a specific order, creating a chain of amino acids. Glycyl-tRNA synthetase plays a role in the addition of glycine in the appropriate place in the protein chain of amino acids. Several mutations have been identified in the GARS gene in individuals with distal motor neuropathy type V. These mutations change individual amino acids in the coding of glycyl-tRNA synthetase. Although it is unclear how these genetic mutations lead to disease, it is likely to reduce the activity of glycyl-tRNA synthetase, which may impair the transmission of nerve impulses.
Motor neuropathy distal V type 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 distal motor neuropathy type V, by complete PCR amplification of the exons of BSCL2 and GARS, 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).