In rare cases -- for instance, among siblings in two families from Pakistan and Oman described in a new study -- children have been born with an unnamed neurological disorder. Now researchers have not only identified the genetic mutations involved, but also replicated them in lab cultures and mouse models to produce an initial understanding of how the mutations cause the disease. The study, published online in the Proceedings of the National Academy of Sciences, highlights both new medical and scientific opportunities, said Eric Morrow (photo), M.D., Ph.D., Associate Professor of Biology and of Psychiatry and Human Behavior in the Warren Alpert Medical School of Brown University. "This is a clear, new neurogenetic disorder due to mutations in GPT2," said Dr. Morrow, who also sees patients at Bradley Hospital and is affiliated with the Brown Institute for Brain Science. "In addition to the relevance this has to the diagnosis of developmental disorders, and potentially therapeutics, it is also a window into how the brain develops and how the brain functions." The PNAS paper reveals specific findings of basic neurodevelopment, Dr. Morrow said. The gene at issue, GPT2 (glutamic--pyruvic transaminase 2), is expressed in the nucleus of cells, but the enzyme it generates appears vital to metabolic pathways in the mitochondria, organelles which provide energy and biosynthetic building blocks to cells. The consequences of the mutations appear to be in leaving developing brains without biosynthetic abilities to grow properly, and with deficits in metabolites that could help prevent degeneration. Moreover, the G in the gene name stands for glutamate, an important neurotransmitter that governs how neurons connect and interact.
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