Researchers identify new gene that may increase risk of ALS
MINNEAPOLIS – Researchers have identified a new gene that may increase a person’s risk of developing ALS, according to a new study published in the June 16, 2021 online issue of Neurology®, the medical journal of the American Academy of Neurology. The gene, called TP73, produces a protein that helps regulate the life cycle of a cell. Researchers have found that some people with ALS have mutations in this gene and that the mutations can interfere with the health of nerve cells.
ALS is a rare and progressive neurodegenerative disease that affects nerve cells in the brain and spinal cord. People with ALS lose the ability to initiate and control muscle movement, often resulting in total paralysis and death.
Genetic and environmental factors can contribute to the development of ALS. About 15% of cases are diagnosed as familial ALS, which is when a person has more than one family member who has also had the disease. Cases with no known genetic cause are called sporadic ALS.
“Much remains unknown about the genetics and the processes that lead to the development of ALS,” said study author Lynn B. Jorde, PhD, of the University of Utah in Salt Lake City. “Although known genetic variants are critical determinants of 68% of familial ALS cases, they represent only 17% of sporadic ALS cases, but up to 61% of sporadic ALS cases are thought to be influenced by genetic factors. risk factor for sporadic ALS, rare mutations in the TP73 gene. We also found that mutations in this gene adversely affect protein function and that the protein created by this gene is necessary for healthy nerve cells.
For the study, 87 people with sporadic ALS provided blood samples. The researchers used a technique called exome sequencing to examine the genes that code for each participant’s proteins. In this group, the researchers found that five people had rare mutations in the TP73 gene.
The researchers then looked at two more groups with sporadic ALS, totaling nearly 2,900 people, and found 19 more people with rare mutations in the TP73 gene.
When the researchers looked at the genes of a control group of 324 people without ALS, they found no mutations in TP73.
In the lab, the researchers performed additional experiments on cells and found that when there were mutations in the TP73 gene, it led to abnormal cell differentiation and increased cell death. They also used CRISPR gene editing technology to delete the TP73 gene and found that this resulted in impaired development of nerve cells, similar to what is seen in ALS.
“Taken together, our results strongly suggest that mutations in the TP73 gene increase the risk of ALS,” Jorde said. “Our research indicates that cell death linked to these mutations may be a factor in the development of ALS. This finding provides a new target for researchers working to develop therapies to slow or even stop the progression of ALS.”
The study was supported by the National Institutes of Health and Target ALS.
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