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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2016,9,20]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>\n                    We report autosomal recessive mutations in the enzyme glutamate pyruvate transaminase 2 (GPT2) in a neurological syndrome involving intellectual disability, reduced brain growth, and progressive motor symptoms. We show that the mutations inactivate the enzyme. GPT2 catalyzes the reversible addition of an amino group from glutamate to pyruvate, yielding alanine and \u03b1-ketoglutarate. The\n                    <jats:italic>GPT2<\/jats:italic>\n                    gene demonstrates expression in brain postnatally, and the protein localizes to mitochondria. As in humans,\n                    <jats:italic>Gpt2<\/jats:italic>\n                    -null mice exhibit reduced brain growth. Furthermore, mutant mouse brains show abnormal metabolite levels, including in pathways involving amino acid metabolism, the TCA cycle, and neuroprotective mechanisms. Our study identifies GPT2 as an important mitochondrial enzyme in disease that has general relevance to developmental and potentially to neurodegenerative mechanisms.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1609221113","type":"journal-article","created":{"date-parts":[[2016,9,6]],"date-time":"2016-09-06T21:55:26Z","timestamp":1473198926000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":70,"title":["Mutations in mitochondrial enzyme GPT2 cause metabolic dysfunction and neurological disease with developmental and progressive features"],"prefix":"10.1073","volume":"113","author":[{"given":"Qing","family":"Ouyang","sequence":"first","affiliation":[{"name":"Department of Molecular Biology, Cell Biology, and Biochemistry, Brown University, Providence, RI 02912;"},{"name":"Institute for Brain Science, Brown University, Providence, RI 02912;"},{"name":"Developmental Disorders Genetics Research Program, Emma Pendleton Bradley 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