@article {410,
	title = {Impaired Amino Acid Transport at the Blood Brain Barrier Is a Cause of Autism Spectrum Disorder.},
	journal = {Cell},
	volume = {167},
	year = {2016},
	month = {2016 Dec 01},
	pages = {1481-1494.e18},
	abstract = {<p>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.</p>},
	keywords = {Amino Acids, Animals, Autism Spectrum Disorder, Blood-Brain Barrier, Brain, Female, Humans, Infant, Infant, Newborn, Large Neutral Amino Acid-Transporter 1, Male, Mice, Mice, Knockout, Mutation, Pedigree, Protein Biosynthesis, Receptor, TIE-2},
	issn = {1097-4172},
	doi = {10.1016/j.cell.2016.11.013},
	author = {T{\u a}rlungeanu, Dora C and Deliu, Elena and Dotter, Christoph P and Kara, Majdi and Janiesch, Philipp Christoph and Scalise, Mariafrancesca and Galluccio, Michele and Tesulov, Mateja and Morelli, Emanuela and Sonmez, Fatma Mujgan and Bilguvar, 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 E and {\c C}a{\u g}layan, Ahmet Okay and G{\"u}nel, Murat and Gleeson, Joseph G and Novarino, Gaia}
}
@article {161,
	title = {Inactivating mutations in MFSD2A, required for omega-3 fatty acid transport in brain, cause a lethal microcephaly syndrome.},
	journal = {Nat Genet},
	volume = {47},
	year = {2015},
	month = {2015 Jul},
	pages = {809-13},
	abstract = {<p>Docosahexanoic acid (DHA) is the most abundant omega-3 fatty acid in brain, and, although it is considered essential, deficiency has not been linked to disease. Despite the large mass of DHA in phospholipids, the brain does not synthesize it. DHA is imported across the blood-brain barrier (BBB) through the major facilitator superfamily domain-containing 2a (MFSD2A) protein. MFSD2A transports DHA as well as other fatty acids in the form of lysophosphatidylcholine (LPC). We identify two families displaying MFSD2A mutations in conserved residues. Affected individuals exhibited a lethal microcephaly syndrome linked to inadequate uptake of LPC lipids. The MFSD2A mutations impaired transport activity in a cell-based assay. Moreover, when expressed in mfsd2aa-morphant zebrafish, mutants failed to rescue microcephaly, BBB breakdown and lethality. Our results establish a link between transport of DHA and LPCs by MFSD2A and human brain growth and function, presenting the first evidence of monogenic disease related to transport of DHA in humans. </p>},
	keywords = {Adolescent, Animals, Biological Transport, Blood-Brain Barrier, Brain, Case-Control Studies, Child, Child, Preschool, Consanguinity, Fatty Acids, Omega-3, Female, Genes, Lethal, Genetic Association Studies, HEK293 Cells, Humans, Infant, Male, Mice, Knockout, Microcephaly, Mutation, Missense, Syndrome, Tumor Suppressor Proteins, Zebrafish},
	issn = {1546-1718},
	doi = {10.1038/ng.3311},
	author = {Guemez-Gamboa, Alicia and Nguyen, Long N and Yang, Hongbo and Zaki, Maha S and Kara, Majdi and Ben-Omran, Tawfeg and Akizu, Naiara and Rosti, Rasim Ozgur and Rosti, Basak and Scott, Eric and Schroth, Jana and Copeland, Brett and Vaux, Keith K and Cazenave-Gassiot, Amaury and Quek, Debra Q Y and Wong, Bernice H and Tan, Bryan C and Wenk, Markus R and G{\"u}nel, Murat and Gabriel, Stacey and Chi, Neil C and Silver, David L and Gleeson, Joseph G}
}
