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 online edition of Neurology® on 16. The gene called TP73 produces a protein that helps improve the life cycle of an Regulate cell. Researchers found that some people with ALS have mutations in this gene and that the mutations can affect nerve cell health.
ALS is a rare, progressive neurodegenerative disease that affects nerve cells in the brain and spinal cord. People with ALS lose the ability to initiate and control muscle movements, which often leads to total paralysis and death.
Both 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 also had the disease. Cases with no known genetic cause are known as sporadic ALS.
Much is still unknown about the genetics and processes that lead to the development of ALS. While known gene variants are critical determinants of 68% of familial ALS cases, they make up only 17% of sporadic ALS, yet it is assumed that up to 61% of sporadic ALS are influenced by genetic factors. Our study identified a new genetic risk factor for sporadic ALS, rare mutations in the TP73 gene. We also found that mutations in this gene have a deleterious effect on protein function and that the protein made by this gene is necessary for nerve cell health.
Study author Lynn B. Jorde, PhD, from the University of Utah at Salt Lake City. “
87 people with sporadic ALS provided blood samples for the study. The researchers used a technique called exome sequencing to examine the protein-coding genes for each participant. 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, a total of nearly 2,900 people, and found another 19 people with rare mutations in the TP73 gene.
When the researchers examined the genes of a control group of 324 people without ALS, they found no mutations in TP73.
In the laboratory, the researchers conducted additional experiments on cells and found that mutations in the TP73 gene led to abnormal cell differentiation and increased cell death. They also used CRISPR gene editing technology to remove the TP73 gene and found that this led to impaired development of nerve cells, similar to what happens with ALS.
Taken together, our results strongly suggest that mutations in the TP73 gene increase the risk of ALS. Our research shows that the cell death associated with these mutations can be a factor in the development of ALS. This discovery offers a new target for researchers working to develop therapies to slow or even stop the progression of ALS.
Lynn B. Jorde, PhD
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The study was supported by the National Institutes of Health and Target ALS.
