Question: What are the genetic changes related to distal hereditary motor neuropathy, type V ?
Answer: Mutations in the BSCL2 and GARS genes cause distal hereditary motor neuropathy, type V. The BSCL2 gene provides instructions for making a protein called seipin, whose function is unknown. Mutations in the BSCL2 gene likely alter the structure of seipin, causing it to fold into an incorrect 3-dimensional shape. Research findings indicate that misfolded seipin proteins accumulate in the endoplasmic reticulum, which is a structure inside the cell that is involved in protein processing and transport. This accumulation likely damages and kills motor neurons (specialized nerve cells in the brain and spinal cord that control muscle movement), leading to muscle weakness in the hands and feet. The GARS gene provides instructions for making an enzyme called glycyl-tRNA synthetase, which is involved in the production (synthesis) of proteins. It is unclear how GARS gene mutations lead to distal hereditary motor neuropathy, type V. The mutations probably reduce the activity of glycyl-tRNA synthetase. A reduction in the activity of this enzyme may impair transmission of nerve impulses. As a result, nerve cells slowly lose the ability to communicate with muscles in the hands and feet. Mutations in other genes may also cause distal hereditary motor neuropathy, type V.
Source: GHR