Hereditary sensory and autonomic neuropathy type V (Hereditary sensory and autonomic neuropathy type V -HSAN5-) - Gen NGF.
Hereditary sensory and autonomic neuropathy type V (HSAN5) is a disease that primarily affects sensory neurons that transmit information about sensations such as pain, temperature and touch. In general, the signs and symptoms of the disease appear at birth or during childhood. Affected individuals lose the ability to feel pain, heat and cold. The perception of pain, the feeling of pain from injuries in bones, ligaments or muscles, is particularly affected in people with HSAN5. Because of the inability to feel pain, affected individuals suffer repeated serious injuries such as bone fractures and joint injuries that go unnoticed. Repeated trauma can lead to a condition called Charcot joints in bones and tissues surrounding the joints are destroyed.
This process is due to mutations in the NGF gene, located on the short arm of chromosome 1 (1p13.1). This gene encodes a protein called nerve growth factor beta (NGF?). This protein is important in the development and survival of neurons, especially sensory neurons. This protein acts by binding to its receptors, thereby initiating signaling within the cell. The NGF? protein may bind to two different receptors, the receptor NTRK1 or p75NTR receptor. Both receptors are found on the surface of sensory neurons and other neurons. Binding of protein NGF? receptor NTRK1 signals causes these neurons to grow and mature and assume specialized functions. This binding also blocks signals that initiate the process of apoptosis. In addition, signaling through NTRK1 NGF? plays a role in pain sensation. Studies suggest that p75 signaling can help grow and differentiate sensory neurons, but can also trigger apoptosis.
It has identified at least one mutation in the gene of NGF which results in hereditary sensory and autonomic neuropathy type V (HSAN5). This mutation changes one amino acid in the protein NGF?. Specifically, the amino acid arginine is replaced by the amino acid tryptophan at position 100 (R100W or Arg100Trp). This change causes the mutated protein NGF? can not bind to p75NTR receptor and alters the signaling through the receptor NTRK1. In addition, people with HSAN5 have a small number of sensory neurons. However, it is unclear the mechanism by which NGF gene mutation leads to an inability to feel pain and temperature sensitivity. Although NGF? protein is important in many types of neurons, sensory neurons just seem to be affected in people with HSAN5.
This disease is inherited in an autosomal recessive pattern, that is, both copies of the gene in every cell must have mutations for alteration is expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually show no signs and symptoms of the disease.
Tests in IVAMI: in IVAMI perform detection of mutations associated with hereditary sensory neuropathy and autonomic type V (HSAN5), by complete PCR amplification of the exons of the NGF gene, and subsequent sequencing.
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).