Nat Med: Neurological abnormalities lead to rare genetic diseases.

September 29, 2020 /--- A recent study identified neuron activity abnormalities in patients with rare genetic diseases.
, the authors found that overexpressive expression of specific genes and the treatment of several antipsychotic drugs helped restore normal cellular function.
study, funded by the National Institutes of Health (NIH) and published in the journal Nature Medicine, sheds light on the factors that lead to the development of mental illness caused by 22q11.2 deficiency syndrome.
22q11.2 deficiency syndrome is caused by the absence of genetic material on chromosome 22 q11. 2.
people with 22q11.2 deficiency syndrome have symptoms such as abnormal heart, poor immune function, abnormal upper jaw development, bone differences, and stunting.
addition, this genetic mutation increased the risk of autism spectrum disorder (ASD) by 20-30% and the risk of mental illness by 30 times.
22q11.2 deficiency syndrome is the most common variant of the number of copies of genes found in ASD patients, and up to a quarter of people with this genetic syndrome develop schizophrenia spectrum disorder.
(Photo: www.pixabay.com) "This is the largest study of its kind in terms of the number of patients who donated cells and is important for studying key genetic risk factors for this type of mental illness," said Dr. David Panchision, who led the study.
can successfully control some of the effects of this genetic syndrome, such as cardiovascular and immune abnormalities, it is more challenging to address the associated psychotic effects.
partly because little is understood about the underlying neurological cell defects that cause mental illness.
To study the neural pathps associated with mental illness in patients with 22q11.2 deficiency syndrome, Dr. Sergiu Pasca, M.D., an associate professor of psychiatry and behavioral sciences at Stanford University in California, and researchers from several other universities and research institutes collected 15 patients with 22q11.2 and 15 healthy control samples to create induced omnicnicnics.
used these cells to create three-dimensional brain-like organs that outline key features of the development of the human cerebral cortical layer.
" These brain 3-D cell models can self-organize, for example, if directed into a cortical layer similar to the brain, they contain deep and shallow functional glutamate-energy neurons and non-reactive star-shaped glial cells, and can maintain this state.
, these patient-derived models have great potential to study neuropsycological disorders.
analyzed gene expression in organs throughout the 100-day development process.
they found changes in gene expression in organs associated with neuron excitability.
these changes prompted researchers to examine the characteristics of these neurons associated with electrical signal conduction and communication.
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when calcium ions, etc., pass in and out of cells through small channels in the cell membrane, an electric charge is generated.
researchers imaged thousands of cells and recorded electrical activity from hundreds of neurons from individuals with 22q11.2 deficiency syndrome, and found abnormalities in the way calcium enters and moves out of cells.
a gene called DGCR8 is missing from 22q11.2 deficiency syndrome.
researchers found that the loss of a copy of the gene was enough to induce excitable changes in neurons.
In addition, 22q11.2 missing syndrome neurons are treated with one of three antipsychotic drugs (reclobili, Shubili, or O nitrogen flat), which restores defects in the neuron resting membrane potetics within minutes.
(bioon.com) Source: Study sheds light on abnormal neural function in rare genetic disorder Original source: Neuronal defects in a human cellular model of 22q11.2 deletion syndrome, Nature Medicine (2020). DOI: 10.1038/s41591-020-1043-9 ,