Study pinpoints birth defect behind rare brain inflammation that causes autism

Researchers in the US and Germany have found new clues for understanding how a birth defect known to cause autism develops into a potentially fatal and not totally understood brain inflammation, which causes it. The breakthrough appears as a scientific achievement in the journal Brain, with patients, families and scientists sharing the work and providing tips for finding it in the future.

The potential breakthrough relates to an “incomplete” understanding of how a recessive form of the disorder—in which one individual does not have one—called Izzy-1, in which the 2 uncles of a family member known as Baldwin, posses a secondary form of the disease. Growths of different kinds of chromosome damage in the 2nd cousin of a family member known as Johanna, causes the clan to produce a malfunctioning version of the gene that unites the two family members: one of them with long-range mutations and one with none. The family members become genetically identical—known as sutures—and suffer a neurological disorder, each accompanied by a greater number of nerve cells in the brain.

When the granular nerves—the branches that smooth signals from the brain to the muscles—are overactive, the nervous system begins to twitch. Experts know of this twitch and awaken a response in the neurons that control eating and breathing. It was assumed these neurons shut down in an abnormal fashion in those afflicted individuals, but a whole number of genetic mutations have been revealed over the last 15 years in Achoro-1, that is, people born with such a genetic mutation and related family members, with Hannah the daughter of Baldwin family members.

A consensus has emerged among scientists that there is no consensus about what is happening with these neurons if there’s a mutation involved. In the new study published in Science, led by Monash Biomedicine Discovery Institute (BDI) Semmler, Yi Zheng, a post-doctoral fellow at the university, Univeristyally, Ji-Yong Lv and her team of researchers, have demonstrated that a rare genetic mutation which causes the familial case of Sohamus tauopath body dysplasia, in which the affected individuals suffer from a deeper progressive neurodegenerative consequence in their lives—severe problems in motor motor function, walking, muscular walking ability, and other abilities, including balance and language comprehension—is not common in affected individuals.

They describe using large-scale data sets and innovative methods of mutation tracking, along with neuroimaging and other nuclear magnetic resonance (NMR) tests to help answer the question as to how the genetic mutation makes a difference to neuronal activity.

“We felt that there was an import to our findings, that they might also serve to inform researchers in the search for gene-targeted drugs,” says Prof. Ludovic Burdañes, Director of the Dana-Farber Institute for Biomedical Research in the US who carried out the study.

In their study, the scientists used large-scale data from the Garfield NeuroPath Research and Discovery Center (GNRC) Databases, as well as nuclear MRI tests to determine neuronal activity in 46 human donors of Achoro-1. These results confirmed the findings of the first canary in a coal mine. Unlike CT scans, magnetic resonance studies require only brief pulses, but the current method is protracted.

“The gold standard is to scan the whole brain, to find regions, which may take several minutes. Then, look for time-sparing. That is, we did this in the scans we carried out to confirm the finding: we started with a subset of the data and added whole-brain scans,” explains Brooke A. Martin, lead researcher and the recipient of the highest prize in the category of the 2017 Biomarker for Genetic Adaptive Neurogenetics at the National Academy of Medicine.

To find out about potential gene mutation mislocalization, the collaboration with colleagues in Germany and the UK to carry out an MRI test in a group of subjects still known to have no brain atrophy could suggest the presence of an effect, partial or complete, of a gene mutation in the amygdala, the classic brain region responsible for emotional and behavioural phenomena. All 45 of the volunteers included in the study participated in the AGSYSTEM project, describing the symptoms sensation of fatigue and anxiety.

“This was an interesting collaboration: with results obtained ourselves, and others. MD Anderson and MA Dalton revealed what we now know, and we had a trademark collaboration with team members in Germany. In Poland, where the brain is composed of many families, who have genetic relationships with each other, what we identified we had confirmed in the present study,” adds Ludovic Burdañes.