Nat Genet: multiple mutations of a single gene can cause multiple damages to brain cells

December 22, 2019 / bioun / -- researchers in Sinai mountain found that different mutations of a single gene may have multiple effects on a person's health, indicating that gene therapy may need to do more than just supplement the missing or dysfunctional egg white that the gene should code The results were published in Nature Genetics Dr Kristen brennand, associate professor of genetics and genomics, neuroscience and psychiatry at the Icahn School of medicine in Mount Sinai, said: "we must fully understand the mutation in order to understand its repair." (image source: www Pixabay Com) this collaboration is based on Dr brennand's interest in neuropathogenic gene neurexin-1 (NRXN) and Dr Fang's technology in using complex techniques to analyze different forms of individual genes Schizophrenia, autism and bipolar patients sometimes carry mutations in nrxn1 Dr brennand said: "up to now, nrxn1 has been basically studied only in mice, and based on mouse research, we know that there are more than 300 splicing homotypes This means that the gene produces 300 different proteins in mice " The team set out to understand how nrxn1 works in human neurons and how different mutations affect cell function Dr brennand and his team collected skin samples from several patients at Sinai Mountain hospital They diagnosed the patients with mental health, and then they used these samples and samples from healthy participants to culture human induced pluripotent stem cells (hiPSC), which have the ability to grow in any cell in the body Using IPSC, we induced cells to grow into neurons In cells from patients with nrxn1 mutations, scientists pointed out differences in the shape and electrical activity of neurons and the rate at which they mature But that's not all Everyone has two copies of the gene If mutations are present, they are usually only present in one of these copies Normal, untransformed genes still produce healthy proteins, but the mutated copies cannot produce any proteins, which means that the individual produces fewer proteins than are needed for normal function Researchers believe that introducing more healthy proteins can save neurons, but not always Some mutations cause the second copy of the gene to produce a specific mutation for the protein The researchers found that these mutated proteins may interfere with the function of healthy proteins The team found that even those cells that produce healthy proteins that function properly enough, if there is a mutated form of the protein at the same time, they can develop symptoms - and different mutations lead to different symptoms "In terms of function, these mutations seem to have a significant negative effect," Dr brennand said The study was small, and the team studied very few genetic variants In the future, it will be important to understand how mutations affect protein function Sources of information: different mutations in a single gene can wreak many types of havoc in brain cells origin: Erin Flaherty, Shijia Zhu, Natalie Barretto, Esther Cheng, P J Michael deans, Michael B Fernando, Nadine schrode, Nancy Francoeur, Alesia Antoine, Khaled alganem, Madeline Halpern, gintaras deikus, hardik Shah, Megan Fitzgerald, Ian Ladran, Peter Gochman, Judith Rapoport, Nadejda M Tsankova, Robert McCullumsmith, Gabriel E Hoffman, Robert Sebra, Gang Fang, Kristen J Brennand Neuronal impact of patient-specific aberrant NRXN1α splicing Nature Genetics , 2019; 51 (12): 1679 DOI: 10.1038/s41588-019-0539-z