Thanks to study teams on opposite sides of the world, an uncommon but potentially severe brain condition now has a precise cause. The illness, known as hypomyelinating leukodystrophy, is caused by a mutation in the gene that regulates the movement of zinc, an essential dietary element, out of cells. The study was published in the journal Brain by Dr. Quasar Padiath of the University of Pittsburgh and Dr. Anju Shukla of the Kasturba Medical College in India.
This is the first time a mutation in a zinc transporter gene, TMEM163, has been firmly related to the development of any brain illness, and it has the potential to shed light on the role of zinc in normal brain development, damage, and disease. “Discovering a novel gene that causes a disease is always exciting; that feeling never goes old,” said Padiath, an associate professor of human genetics and neuroscience at Pitt. “And discovering that a zinc transporter is critical for normal myelin development could have various clinical ramifications and lead to new treatments for other neurological diseases.”
Hypomyelinating leukodystrophies are rare and often deadly neurological illnesses caused by mutations in genes involved in the formation or maintenance of myelin, the fatty layer of insulation that surrounds nerves and aids in the transmission of electrical impulses. As the myelin layer thins and disappears in these people, nerve signals come to a crawl, resulting in a plethora of neurological issues such as decreased movement and balance control, muscle wasting, vision impairments, hearing loss, and memory loss.
While genes have been linked to leukodystrophies, the bulk of cases’ genetic origins remain unclear. Clinical neurologists frequently consult with researchers like Padiath to determine the underlying reason of a patient’s problem and propose the best course of treatment.
Padiath searches for mutations in patients’ genomes and studies the effects of these mutations in cells and animal models such as mice. Such an analysis is no easy task. Multiple independent patient cases with the same gene deficiency and clinical presentation must be identified in order to reliably link a new gene mutation to illness symptoms.
Finding cases of rare disorders, such as hypomyelinating leukodystrophies, requires tapping into a global network of scientific and clinical collaborators. The first patient sample for this investigation came from Shukla, a professor of medical genetics at Manipal University in southwest India. Inquiries to other organizations in the United States and the Netherlands revealed that additional families had mutations in the same gene.
A series of in-depth lab investigations revealed that the TMEM163 mutations impede the transporter’s capacity to properly shunt zinc from within the cell, resulting in decreased production of proteins necessary for myelin creation and maintenance and increased cell death.
“Understanding how genes generate rare diseases is the first step toward discovering remedies,” Padiath added. “It is crucial to remember that uncommon diseases are very significant and real for patients and their families; studying these diseases helps identify solutions and gives patients hope, as well as valuable insights into therapeutic targets required for normal cell functioning.”
SOURCE: Scientists discover novel mechanism that causes rare brain disease (medicalxpress.com)