Medical research Painlessness caused by gene mutation

Mutated genes cause pain insensitivity
In some people, a rare gene mutation leads to pain insensitivity. However, what sounds like a blessing involves some risks for those affected. For example, injuries and illnesses would often not be recognized or only detected very late, reports MedUni Vienna. According to the international research team led by Michaela Auer-Grumbach from the University Clinic for Orthopedics at the Medical University of Vienna, the PRDM12 gene plays a decisive role in the reduced sensation of pain.

The research team of the MedUni Vienna, the University of Munich and the University of Cambridge has analyzed the genetic material of patients without pain perception in their study and were able to identify mutations of the PRDM12 gene as a cause of analgesia. Further research should now show "how far the findings on PRDM12 are relevant for pain research and the development of new pain medications," reports Michaela Auer-Grumbach. The results of the current study were published in the journal "Nature Genetics".

Bone fractures are often noticed late in patients with a lack of pain. (Image: stockdevil / fotolia.com)

Pain insensibility often leads to injuries
According to the researchers, the starting point of their investigations were two unrelated children with a very rare, unusual disease. Both showed no sensation of pain from birth. In everyday life, this has fatal consequences. "The affected children are usually at the time of breaking the first teeth on the fact that they hurt themselves tongue, lips and fingers, and even bite off parts of it," says Michaela Auer-Grumbach ... Also "it comes very easy to bone fractures, often go unnoticed for a long time because of the lack of pain, "explains the first author of the study. In many cases the freedom from pain leads to unnoticed injuries, burns and broken bones in the course of their lives, which are recognized late because of the lack of pain control and heal badly. Without proper medical care, the worst would be deadly complications.

Mutations of the PRDM12 gene
In the analysis of the entire exome (all sections of the genetic material that encode proteins) of the two children, the researchers noticed mutations in the gene PRDM12. "The detection of mutations in the same gene in two persons from different families with a very similar clinical picture was already a strong indication that we had discovered the responsible gene," explains Jan Senderek from the Friedrich Baur Institute of the University of Munich. The working group of Geoffrey Woods at the University of Cambridge then provided the final proof. "They were also able to demonstrate PRDM12 mutations in patients with congenital analgesia," according to the MedUni Vienna report. In the study of additional patients with congenital pain perception disorders, the scientists, in collaboration with colleagues from home and abroad, came up with further mutations.

Impaired development of the nervous system?
In order to understand the mechanism of the disease, the scientists, together with development biologists from the University of Tokyo, have investigated the function of PRDM12 using frog larvae, according to the MedUni Vienna. In animals, the loss of PRDM12 has led to the defective development of nerve cells that are important for pain perception. According to the researchers, the gene PRDM12 "contains the information for a factor that determines the activity of other genes and thus the development of cells and tissues." This suggests that the failure of PRDM12 leads to a false control of previously unknown target genes , which in turn are necessary for the development of the nervous system and a functioning pain perception.

Insights into how the pain senses
According to Michaela Auer-Grumbach, the discovery of the cause of the lack of pain also enables a "targeted genetic diagnosis and consultation of affected patients and their families". Although no promising therapy has been available so far, supportive measures, education and training of those affected and their families can significantly reduce the risk of serious injuries and complications. In addition, the study authors hope for increased attention from doctors and geneticists for the very rare and still little-known clinical picture. The fact that disorders of factors that control the genome, can lead to pain insensitivity, was new and allow insights into the development of the nervous system and the functioning of the pain sensation. (Fp)