@article{1183, abstract = {Autism spectrum disorders (ASD) are a group of genetic disorders often overlapping with other neurological conditions. We previously described abnormalities in the branched-chain amino acid (BCAA) catabolic pathway as a cause of ASD. Here, we show that the solute carrier transporter 7a5 (SLC7A5), a large neutral amino acid transporter localized at the blood brain barrier (BBB), has an essential role in maintaining normal levels of brain BCAAs. In mice, deletion of Slc7a5 from the endothelial cells of the BBB leads to atypical brain amino acid profile, abnormal mRNA translation, and severe neurological abnormalities. Furthermore, we identified several patients with autistic traits and motor delay carrying deleterious homozygous mutations in the SLC7A5 gene. Finally, we demonstrate that BCAA intracerebroventricular administration ameliorates abnormal behaviors in adult mutant mice. Our data elucidate a neurological syndrome defined by SLC7A5 mutations and support an essential role for the BCAA in human brain function.}, author = {Tarlungeanu, Dora-Clara and Deliu, Elena and Dotter, Christoph and Kara, Majdi and Janiesch, Philipp and Scalise, Mariafrancesca and Galluccio, Michele and Tesulov, Mateja and Morelli, Emanuela and Sönmez, Fatma and Bilgüvar, Kaya and Ohgaki, Ryuichi and Kanai, Yoshikatsu and Johansen, Anide and Esharif, Seham and Ben Omran, Tawfeg and Topcu, Meral and Schlessinger, Avner and Indiveri, Cesare and Duncan, Kent and Caglayan, Ahmet and Günel, Murat and Gleeson, Joseph and Novarino, Gaia}, journal = {Cell}, number = {6}, pages = {1481 -- 1494}, publisher = {Cell Press}, title = {{Impaired amino acid transport at the blood brain barrier is a cause of autism spectrum disorder}}, doi = {10.1016/j.cell.2016.11.013}, volume = {167}, year = {2016}, }