Researchers from different fields working on different sides of the world have found out what causes a rare brain disorder that can be very painful. The disorder, known as hypomyelinating leukodystrophy, is caused by a mutation in the gene that regulates the transport of zinc out of cells, an important dietary micronutrient. Dr. Quasar Padiath of the University of Pittsburgh and Dr. Anju Shukla of the Kasturba Medical College in India worked together on the study, which was published in the journal Brain.
It has the potential to shed light on the function of zinc in healthy brain development, injury, and disease. This is the first time that a change in a zinc transporter gene, TMEM163 in this case, has been proven to cause a brain disorder.
Padiath, an associate professor of human genetics and neurobiology at Pitt, said that finding a new gene that causes a disease is exciting and never gets old. The study also says that finding out that a zinc transporter is important for the development of myelin “could have many clinical implications and offer new ways to treat other neurological conditions.”
Neurological disorders known as hypomyelinating leukodystrophy, which are rare and frequently fatal, are brought on by errors in genes that are involved in the development or maintenance of myelin, the fatty layer of insulation that surrounds nerves and aids in the transmission of electrical impulses. As the myelin layer gradually thins and disappears in these patients, nerve signals slow down to a crawl. This causes a number of neurological problems, such as trouble controlling movement and balance, muscle loss, vision problems, hearing loss, and memory loss.
Leukodystrophies have genetic roots, but for the vast majority of cases, these roots are still unknown. Clinical neurologists often talk to researchers like Padiath to figure out what’s really wrong with a patient and how to treat them best.
Padiath searches the genomes of patients for mutations and examines the consequences of these mutations in cells and mouse models. Such an analysis is a difficult task. To prove that a new gene mutation causes disease symptoms, there must be more than one case of a different patient with the same gene defect and clinical presentation.
Finding such cases of rare diseases like hypomyelinating leukodystrophy is only possible by utilizing a global network of scientific and clinical collaborators. The first patient sample used in this study was provided by Shukla, a professor of medical genetics at Manipal in southwest India. Through questions to other groups in the U.S. and the Netherlands, more families with the same gene mutation were found.
Several careful lab tests showed that the TMEM163 mutations make it harder for the transporter to move zinc out of the cell. This leads to less production of proteins that are needed for making myelin and keeping it in good shape, as well as more cell death.
Finding treatments begins with understanding how genes contribute to rare diseases, according to Padiath. “It is crucial to keep in mind that, even though they may be uncommon on a global scale, certain diseases have a significant impact on patients and their families. Researching these illnesses contributes to the discovery of treatments, offers patients hope, and provides important information about therapeutic targets crucial for healthy cell function. “
