Impaired Amino Acid Transport at the Blood Brain Barrier Is a Cause of Autism Spectrum Disorder
Tărlungeanu DC, Deliu E, Dotter CP, Kara M, Janiesch PC, Scalise M, Galluccio M, Tesulov M, Morelli E, Sonmez FM, Bilguvar K, Ohgaki R, Kanai Y, Johansen A, Esharif S, Ben-Omran T, Topcu M, Schlessinger A, Indiveri C, Duncan KE, Caglayan AO, Gunel M, Gleeson JG, Novarino G. Impaired Amino Acid Transport at the Blood Brain Barrier Is a Cause of Autism Spectrum Disorder. Cell 2016, 167: 1481-1494.e18. PMID: 27912058, PMCID: PMC5554935, DOI: 10.1016/j.cell.2016.11.013.Peer-Reviewed Original ResearchConceptsBlood-brain barrierBrain barrierBrain amino acid profilesLarge neutral amino acid transporterAutism spectrum disorderAdult mutant miceBranched-chain amino acid (BCAA) catabolic pathwaySevere neurological abnormalitiesNeutral amino acid transporterIntracerebroventricular administrationNeurological syndromeNeurological abnormalitiesNeurological conditionsSpectrum disorderSLC7A5 geneMotor delayAmino acid transportAmino acid transportersMutant miceNormal levelsBrain functionHuman brain functionEndothelial cellsHomozygous mutationCauses of ASDA novel de novo mutation in ATP1A3 and childhood-onset schizophrenia
Smedemark-Margulies N, Brownstein CA, Vargas S, Tembulkar SK, Towne MC, Shi J, Gonzalez-Cuevas E, Liu KX, Bilguvar K, Kleiman RJ, Han MJ, Torres A, Berry GT, Yu TW, Beggs AH, Agrawal PB, Gonzalez-Heydrich J. A novel de novo mutation in ATP1A3 and childhood-onset schizophrenia. Molecular Case Studies 2016, 2: a001008. PMID: 27626066, PMCID: PMC5002930, DOI: 10.1101/mcs.a001008.Peer-Reviewed Original ResearchRapid-onset dystonia-parkinsonismCommand auditory hallucinationsNovel clinical presentationHemiplegia of childhoodChildhood-onset schizophreniaNovel de novo mutationYr of ageMild motor delayWhole-exome sequencingChromosomal microarray analysisNeuron-specific isoformSodium-potassium pumpClinical presentationDystonia-parkinsonismBehavioral regressionAuditory hallucinationsMotor delayNeuronal functionDe novo mutationsHeterozygous mutationsMutation c.ATP1A3Novo mutationsMicroarray analysisPast functional studies