From the Research
The C.1360A>G variant in the GNE gene is a genetic mutation associated with GNE myopathy, a rare autosomal recessive disorder that causes progressive muscle weakness and atrophy, typically beginning in early adulthood, as supported by the most recent study 1. This mutation specifically changes an adenine (A) to a guanine (G) at position 1360 in the coding sequence, resulting in an amino acid substitution that affects the function of the GNE enzyme. This enzyme is crucial for the biosynthesis of sialic acid, and its dysfunction leads to decreased sialylation of muscle glycoproteins. The clinical significance of this mutation is highlighted by its association with GNE myopathy, characterized by progressive skeletal muscle atrophy, with an estimated prevalence of 1 to 9:1,000, as reported in 2. Key features of GNE myopathy include:
- Progressive muscle weakness and atrophy, typically beginning in early adulthood
- Bilateral foot drop caused by weakness of the anterior tibialis muscles
- Slow progression over decades to involve skeletal muscles throughout the body, with relative sparing of the quadriceps until late stages of the disease
- Histopathologic findings on muscle biopsies include fiber size variation, atrophic fibers, lack of inflammation, and the characteristic "rimmed" vacuoles on modified Gomori trichome staining Currently, there is no approved specific treatment for GNE myopathy, though supportive care including physical therapy, occupational therapy, and mobility aids are recommended to maintain function, as suggested in 3. Genetic counseling is advised for affected individuals and their families, and research on potential treatments including sialic acid supplementation and gene therapy is ongoing, but these remain experimental 1. If you have this variant, it's essential to consult with a neuromuscular specialist and a genetic counselor for personalized management recommendations.