Scoliosis is a condition in which a person’s spine curves sideways, sometimes resembling an ‘S’ or ‘C’. It is the most common childhood musculoskeletal disorder affecting around 0.3% of all children. While mild cases can often be treated or corrected with a back brace, severe cases require surgical correction and affect 1 in every 10,000 children. Most scoliosis cases are considered idiopathic in nature, meaning there is no known cause and it develops spontaneously. Until recently, the majority of the heritability of scoliosis remains undiscovered. Now, a team of researchers from from Missouri have identified a mutation in a gene that is linked to scoliosis and is responsible for maintaining manganese levels in the body.
The team used genetic data from adolescent idiopathic scoliosis (AIS) and controls to identify a single point mutation in a gene called SLC39A8 (solute carrier family 39 member 8) which was associated with a 2 times greater risk of having AIS. This gene is important in controlling the levels of zinc and manganese in the cell. In previous studies, the gene mutation had been linked with changes in body mass, blood pressure, cholesterol, and blood manganese levels. In this study, the mutation was linked to greater spinal curvature, decreased height, higher body mass, and lower blood manganese levels in the AIS group. Additionally, cells with a mutated SLC39A8 had decreased manganese uptake compared to the non-mutated cells. In order to implicate the function of this gene in the development of AIS, the team deleted the gene in zebra fish embryos and monitored the development of their spines. They found that the fish missing the gene had impaired growth, changes in motor activity (movement), and interestingly showed abnormalities in the spine that were similar to scoliosis.
This research highlights the importance of unifying clinical research with basic science and animal models. By integrating the two, the researchers were able to directly implicate this mutation in the abnormal spine development of people with scoliosis. Future studies will need to determine whether manganese supplementation can reduce the incidence of spontaneous scoliosis in teens. This supplementation could be a viable way to prevent a chronic disease and improve the quality of health in many children.
Image Credit: By Lucien Monfils – Own work