Mutations in genes that control the transport of zinc, an essential dietary micronutrient, out of cells cause a disease called dysmyelination leukodystrophy. The study, co-led by Dr. Quasar Padias of the University of Pittsburgh and Dr. Anju Shukla of Kasturba Medical College in India, is reported in the journal. brain.

This is the first time that a zinc transporter gene has been mutated — in this case, TMEM163 — It is critically implicated in the development of all brain disorders and may provide insight into the role of zinc in normal brain development, injury, and disease.

Padius, associate professor of human genetics and neurobiology at Pitt University, said: “Discovering that the zinc transporter is critical for proper myelin development has many clinical implications and may provide new ways to treat other related neurological conditions. I have.

Hypomyelinating leukodystrophy is a rare and often fatal neurological disorder caused by defects in genes involved in the growth or maintenance of myelin. The gradual thinning of the myelin layer, and its loss in these patients, slows nerve signals and contributes to many neurological disorders, including impaired control of movement and balance, muscle wasting, vision problems, and hearing and memory loss. A problem will occur.

Genes have been linked to leukodystrophy, but the genetic basis of the majority of cases is not yet known. Medicine often turns to researchers like Padius.

Padiath combs a patient’s genome looking for mutations and analyzes the effects of these mutations in cells and animal models such as mice. Such analysis is not trivial. Unambiguously linking new genetic variants to disease manifestations requires identification of multiple independent patient cases that share the same genetic defect and clinical presentation.

For rare diseases such as hypomyelinating leukodystrophy, finding such cases requires leveraging a global network of scientific and clinical collaborators. In this study, the first patient sample was from his Shukla, a professor of medical genetics at his Manipal in southwestern India. A survey of other groups in the United States and the Netherlands identified another family with mutations in the same gene.

Through a series of detailed lab studies, TMEM163 Mutations impair the transporter’s ability to effectively shunt zinc from within the cell, reduce production of proteins involved in myelin synthesis and maintenance, and increase cell death.

“Understanding how genes cause rare diseases is the first step in the process of finding a cure,” Padiath said. “It is important to remember that globally rare diseases are of great importance and realism to patients and their families. and help provide valuable insight into therapeutic targets that are essential for normal cell function.”

Story source:

Materials provided University of PittsburghOriginally written by Ana Gorelova. Note: Content may be edited for style and length.