Clinical analysis of 49 patients with congenital nemaline myopathies (NMs), an ultra-rare class of muscle diseases that cause muscle weakness and respiratory distress, revealed a mutational hotspot in one gene that explained the disease in over half of the patients. The new study, published last month in Human Mutation, was led by a team of international scientists seeking to improve diagnostic and prognostic capabilities for NMs. They identified 42 previously unreported gene variants and found that disease severity can be categorized by mutational variant type.
Many NM mutations occur in the NEB gene, which encodes the nebulin protein. Nebulin is a large skeletal muscle protein that controls the length and organization of structural proteins required for muscle contraction. Nebulin mutations cause pathological protein aggregation in skeletal muscle fibers, forming rod-like structures.
Clinical severity ranges widely from infant lethality to a mild disease course that allows patients to lead a fairly normal life. Geneticists struggle to diagnose NMs and predict disease severity because of the NEB gene's large size, nonpathogenic mutations that cause false alarms, repeating gene seq...