Neuromyotonia axonal neuropathy with autosomal recessive (Autosomal recessive axonal neuropathy With neuromyotonia) - Gen HINT1.

Neuromyotonia axonal neuropathy is an autosomal recessive disease affecting peripheral nerves. Peripheral nerves connecting the central nervous system, brain and spinal cord, muscles and sensory cells that detect sensation like touch, pain, heat, and sound. Axonal neuropathy, a characteristic feature of this disease is due to damage to axons, which transmit nerve impulses. In people affected by the disease, this damage leads mainly atrophy of the muscles of the feet, legs and hands. Muscle weakness can lead to exercise intolerance and may cause unusual style of walking, frequent falls, and contractures in hands and feet. In some affected individuals, axonal neuropathy also causes a reduction in sensitivity to touch, heat, or cold, especially in the lower arms or legs. For its part, the characteristic neuromyotonia of this disease leads to hyperexcitability of peripheral nerves, causing a delay in muscle contraction, muscle cramps and mioquimia.

This process is due to mutations in the gene HINT1, located on the long arm of chromosome 5 (5q31.2). This gene encodes protein 1 binding to nucleotide triplet for histidine (HINT1: Histidine triad nucleotide-binding protein). Although the function of this protein is not clear, it is believed to have the ability to bind to nucleotides. HINT1 certain nucleotides decomposes through hydrolysis. However, it is not known if the protein HINT1 performs the same reaction in the body or what effects. Although the mechanisms are not known, the HINT1 protein participates in the nervous system. In neurons, this protein binds to receptors that transmit signals affecting the nervous system function. HINT1 appears to stabilize the interaction of different receptors and regulate effects of signaling. It is also involved in apoptosis. Also, by blocking the activity of certain genes, HINT1 acts as a tumor suppressor.

They have been identified at least 9 mutations in the gene responsible for axonal neuropathy HINT1 autosomal recessive neuromyotonia. Mutations associated change amino acids in the protein HINT1. These changes reduce or eliminate the ability of the protein to carry out the hydrolysis reaction. Sometimes, the altered protein decomposes prematurely. It is unclear how the loss of functional proteins HINT1 affects the peripheral nerves or leads to the signs and symptoms of this disease.

This disease is inherited in an autosomal recessive pattern, which means that 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 axonal neuropathy with autosomal recessive neuromyotonia, by complete PCR amplification of exons HINT1 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).