Posts tagged gene mutation
Articles and news from the latest research reports.
Psychogenic diseases, formerly known as ‘hysterical’ illnesses, can have many severe symptoms such as painful cramps or paralysis but without any physical explanation. However, new research from the University of Cambridge and UCL (University College London) suggests that individuals with psychogenic disease, that is to say physical illness that stems from emotional or mental stresses, do have brains that function differently. The research was published today, 25 February, in the journal Brain.
Psychogenic diseases may look very similar to illnesses caused by damage to nerves, the brain or the muscles, or similar to genetic diseases of the nervous system. However, unlike organic diseases, psychogenic diseases do not have any apparent physical cause, making them difficult to diagnose and even more difficult to treat.
“The processes leading to these disorders are poorly understood, complex and highly variable. As a result, treatments are also complex, often lengthy and in many cases there is poor recovery. In order to improve treatment of these disorders, it is important to first understand the underlying mechanism,” said Dr James Rowe from the University of Cambridge.
The study looked at people with either psychogenic or organic dystonia, as well as healthy people with no dystonia. Both types of dystonia caused painful and disabling muscle contractions affecting the leg. The organic patient group had a gene mutation (the DYT1 gene) that caused their dystonia. The psychogenic patients had the symptoms of dystonia but did not have any physical explanation for the disease, even after extensive investigations.
The scientists performed PET brain scans on the volunteers at UCL, to measure the blood flow and brain activity of both of the groups, and healthy volunteers. The participants were scanned with three different foot positions: resting, moving their foot, and holding their leg in a dystonic position. The electrical activity of the leg muscles was measured at the same time to determine which muscles were engaged during the scans.
The researchers found that the brain function of individuals with the psychogenic illness was not normal. The changes were, however, very different from the brains of individuals with the organic (genetic) disease.
Dr Anette Schrag, from UCL, said: “Finding abnormalities of brain function that are very different from those in the organic form of dystonia opens up a way for researchers to learn how psychological factors can, by changing brain function, lead to physical problems.”
Dr Rowe added: “What struck me was just how very different the abnormal brain function was in patients with the genetic and the psychogenic dystonia. Even more striking was that the differences were there all the time, whether the patients were resting or trying to move.”
Additionally, the researchers found that one part of the brain previously thought to indicate psychogenic disease is unreliable: abnormal activity of the prefrontal cortex was thought to be the hallmark of psychogenic diseases. In this study, the scientists showed that this abnormality is not unique to psychogenic disease, since activity was also present in the patients with the genetic cause of dystonia when they tried to move their foot.
Dr Arpan Mehta, from the University of Cambridge, said: “It is interesting that, despite the differences, both types of patient had one thing in common - a problem at the front of the brain. This area controls attention to our movements and although the abnormality is not unique to psychogenic dystonia, it is part of the problem.”
This type of illness is very common. Dr Schrag said: “One in six patients that see a neurologist has a psychogenic illness. They are as ill as someone with organic disease, but with a different cause and different treatment needs. Understanding these disorders, diagnosing them early and finding the right treatment are all clearly very important. We are hopeful that these results might help doctors and patients understand the mechanism leading to this disorder, and guide better treatments.”
What Causes Lou Gehrig’s Sticky Masses?
Globs of protein clustered in the neurons that control muscles have long been the hallmark of amyotrophic lateral sclerosis (ALS), the fatal neurodegenerative disease also commonly known as Lou Gehrig’s disease. Now, a study of the most commonly found mutant gene in people with ALS reveals an unexpected origin of some of those sticky masses, a finding that may offer drug developers a new target for treatments.
Located on the ninth chromosome, which explains part of its unwieldy name, the C9orf72 gene has a bit of a stutter. A typical version in healthy people contains a stretch of DNA where a string of six genetic letters—GGGGCC—repeats up to 25 times. Scientists have recently found that in a sizable share of people with ALS and frontotemporal dementia (FTD), a less common neurological disease characterized by language, memory, and emotional problems, this repeat occurs many more times; some people have thousands of copies.
Since these C9orf72 mutations were discovered in 2011, some researchers have speculated that the repeats interrupt production of the gene’s normal protein, which serves some as-yet unknown, but vital function in motor neurons or other brain cells. Others have hypothesized that the mutation spawns a large, misshapen strand of RNA that grabs on to proteins such as TDP-43, which normally help process RNA, creating protein tangles that starve the cell of the machinery it needs to function.
Molecular biologists at the Ludwig Maximilians University Munich in Germany and the University of Antwerp in Belgium, however, wondered whether the genetic stutters themselves coded for proteins that became tangled in the cell. Few scientists had considered this because the stutters don’t contain the “start signal” that allows proteins to be made. Still, in a few other diseases caused by genetic repeats, the cell manages to produce proteins from the abnormal gene despite lacking this signal. Sometimes these proteins are toxic and ultimately kill the cell.
Based on the DNA sequence of the GGGGCC-laden C9orf72 seen in ALS and FTD patients, the European team determined that if translated, the gene would produce various proteins containing strings of repeat amino acids. Dubbed dipeptide repeat (DPR) proteins, these molecules don’t normally appear in humans and should be prone to clumping, the scientists concluded. Indeed, when they began to search for DPR protein clusters in actual human brain tissues, they found them in tissue from FTD and ALS patients with the C9orf72 mutation. No such lumps showed up in the brain tissue of healthy controls or ALS and FTD patients without the C9orf72 mutation, increasing the likelihood that the mutation produced them, Dieter Edbauer, a molecular biologist at Ludwig Maximilians, and his co-authors report online today in Science.