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Elsevier, 2019. https://doi.org/10.1016/j.euroneuro.2019.09.039.","ista":"Knaus L, Tarlungeanu D-C, Novarino G. 2019. S.16.03 A homozygous missense mutation in SLC7A5 leads to autism spectrum disorder and microcephaly. European Neuropsychopharmacology. 29(Supplement 6), S11.","mla":"Knaus, Lisa, et al. “S.16.03 A Homozygous Missense Mutation in SLC7A5 Leads to Autism Spectrum Disorder and Microcephaly.” European Neuropsychopharmacology, vol. 29, no. Supplement 6, Elsevier, 2019, p. S11, doi:10.1016/j.euroneuro.2019.09.039.","apa":"Knaus, L., Tarlungeanu, D.-C., & Novarino, G. (2019). S.16.03 A homozygous missense mutation in SLC7A5 leads to autism spectrum disorder and microcephaly. European Neuropsychopharmacology. Elsevier. https://doi.org/10.1016/j.euroneuro.2019.09.039","ama":"Knaus L, Tarlungeanu D-C, Novarino G. S.16.03 A homozygous missense mutation in SLC7A5 leads to autism spectrum disorder and microcephaly. 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Novarino, European Neuropsychopharmacology 29 (2019) S11."}},{"publisher":"Springer Nature","quality_controlled":"1","oa":1,"date_published":"2018-08-07T00:00:00Z","doi":"10.1038/s12276-018-0129-7","date_created":"2019-01-27T22:59:11Z","isi":1,"has_accepted_license":"1","year":"2018","day":"07","publication":"Experimental & Molecular Medicine","article_number":"100","author":[{"last_name":"Tarlungeanu","full_name":"Tarlungeanu, Dora-Clara","first_name":"Dora-Clara","id":"2ABCE612-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","last_name":"Novarino","full_name":"Novarino, Gaia","orcid":"0000-0002-7673-7178"}],"article_processing_charge":"No","external_id":{"pmid":["30089840"],"isi":["000441266700006"]},"title":"Genomics in neurodevelopmental disorders: an avenue to personalized medicine","citation":{"mla":"Tarlungeanu, Dora-Clara, and Gaia Novarino. “Genomics in Neurodevelopmental Disorders: An Avenue to Personalized Medicine.” Experimental & Molecular Medicine, vol. 50, no. 8, 100, Springer Nature, 2018, doi:10.1038/s12276-018-0129-7.","apa":"Tarlungeanu, D.-C., & Novarino, G. (2018). Genomics in neurodevelopmental disorders: an avenue to personalized medicine. Experimental & Molecular Medicine. Springer Nature. https://doi.org/10.1038/s12276-018-0129-7","ama":"Tarlungeanu D-C, Novarino G. Genomics in neurodevelopmental disorders: an avenue to personalized medicine. Experimental & Molecular Medicine. 2018;50(8). doi:10.1038/s12276-018-0129-7","ieee":"D.-C. Tarlungeanu and G. Novarino, “Genomics in neurodevelopmental disorders: an avenue to personalized medicine,” Experimental & Molecular Medicine, vol. 50, no. 8. Springer Nature, 2018.","short":"D.-C. Tarlungeanu, G. Novarino, Experimental & Molecular Medicine 50 (2018).","chicago":"Tarlungeanu, Dora-Clara, and Gaia Novarino. “Genomics in Neurodevelopmental Disorders: An Avenue to Personalized Medicine.” Experimental & Molecular Medicine. Springer Nature, 2018. https://doi.org/10.1038/s12276-018-0129-7.","ista":"Tarlungeanu D-C, Novarino G. 2018. Genomics in neurodevelopmental disorders: an avenue to personalized medicine. Experimental & Molecular Medicine. 50(8), 100."},"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","scopus_import":"1","month":"08","intvolume":" 50","abstract":[{"lang":"eng","text":"Despite the remarkable number of scientific breakthroughs of the last 100 years, the treatment of neurodevelopmental\r\ndisorders (e.g., autism spectrum disorder, intellectual disability) remains a great challenge. Recent advancements in\r\ngenomics, such as whole-exome or whole-genome sequencing, have enabled scientists to identify numerous\r\nmutations underlying neurodevelopmental disorders. Given the few hundred risk genes that have been discovered,\r\nthe etiological variability and the heterogeneous clinical presentation, the need for genotype — along with phenotype-\r\nbased diagnosis of individual patients has become a requisite. In this review we look at recent advancements in\r\ngenomic analysis and their translation into clinical practice."}],"oa_version":"Published Version","pmid":1,"issue":"8","volume":50,"license":"https://creativecommons.org/licenses/by/4.0/","publication_identifier":{"issn":["2092-6413"]},"publication_status":"published","file":[{"file_id":"5893","checksum":"4498301c8c53097c9a1a8ef990936eb5","content_type":"application/pdf","relation":"main_file","access_level":"open_access","file_name":"2018_EMM_Tarlungeanu.pdf","date_created":"2019-01-28T15:18:02Z","file_size":1237482,"date_updated":"2020-07-14T12:47:13Z","creator":"dernst"}],"language":[{"iso":"eng"}],"type":"journal_article","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"status":"public","_id":"5888","file_date_updated":"2020-07-14T12:47:13Z","department":[{"_id":"GaNo"}],"date_updated":"2023-09-11T14:04:41Z","ddc":["570"]},{"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","citation":{"chicago":"Tarlungeanu, Dora-Clara. “The Branched Chain Amino Acids in Autism Spectrum Disorders .” Institute of Science and Technology Austria, 2018. https://doi.org/10.15479/AT:ISTA:th_992.","ista":"Tarlungeanu D-C. 2018. The branched chain amino acids in autism spectrum disorders . Institute of Science and Technology Austria.","mla":"Tarlungeanu, Dora-Clara. The Branched Chain Amino Acids in Autism Spectrum Disorders . Institute of Science and Technology Austria, 2018, doi:10.15479/AT:ISTA:th_992.","short":"D.-C. Tarlungeanu, The Branched Chain Amino Acids in Autism Spectrum Disorders , Institute of Science and Technology Austria, 2018.","ieee":"D.-C. Tarlungeanu, “The branched chain amino acids in autism spectrum disorders ,” Institute of Science and Technology Austria, 2018.","ama":"Tarlungeanu D-C. The branched chain amino acids in autism spectrum disorders . 2018. doi:10.15479/AT:ISTA:th_992","apa":"Tarlungeanu, D.-C. (2018). The branched chain amino acids in autism spectrum disorders . Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:th_992"},"title":"The branched chain amino acids in autism spectrum disorders ","article_processing_charge":"No","author":[{"last_name":"Tarlungeanu","full_name":"Tarlungeanu, Dora-Clara","id":"2ABCE612-F248-11E8-B48F-1D18A9856A87","first_name":"Dora-Clara"}],"publist_id":"7434","project":[{"_id":"25473368-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","grant_number":"F03523","name":"Transmembrane Transporters in Health and Disease"}],"day":"01","year":"2018","has_accepted_license":"1","date_created":"2018-12-11T11:46:14Z","doi":"10.15479/AT:ISTA:th_992","date_published":"2018-03-01T00:00:00Z","page":"88","oa":1,"publisher":"Institute of Science and Technology Austria","ddc":["570","616"],"date_updated":"2023-09-07T12:38:59Z","supervisor":[{"last_name":"Novarino","orcid":"0000-0002-7673-7178","full_name":"Novarino, Gaia","first_name":"Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87"}],"file_date_updated":"2021-02-11T23:30:15Z","department":[{"_id":"GaNo"}],"_id":"395","pubrep_id":"992","status":"public","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"type":"dissertation","language":[{"iso":"eng"}],"file":[{"creator":"dernst","date_updated":"2021-02-11T23:30:15Z","file_size":43684035,"date_created":"2019-04-05T09:19:17Z","file_name":"2018_Thesis_Tarlungeanu_source.docx","access_level":"closed","relation":"source_file","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","embargo_to":"open_access","file_id":"6217","checksum":"9f5231c96e0ad945040841a8630232da"},{"file_name":"2018_Thesis_Tarlungeanu.pdf","date_created":"2019-04-05T09:19:17Z","file_size":30511532,"date_updated":"2021-02-11T11:17:16Z","creator":"dernst","embargo":"2018-03-15","checksum":"0c33c370aa2010df5c552db57a6d01e9","file_id":"6218","content_type":"application/pdf","relation":"main_file","access_level":"open_access"}],"publication_status":"published","degree_awarded":"PhD","publication_identifier":{"issn":["2663-337X"]},"related_material":{"record":[{"relation":"part_of_dissertation","status":"public","id":"1183"}]},"oa_version":"Published Version","acknowledged_ssus":[{"_id":"PreCl"},{"_id":"EM-Fac"},{"_id":"Bio"}],"abstract":[{"text":"Autism spectrum disorders (ASD) are a group of genetic disorders often overlapping with other neurological conditions. Despite the remarkable number of scientific breakthroughs of the last 100 years, the treatment of neurodevelopmental disorders (e.g. autism spectrum disorder, intellectual disability, epilepsy) remains a great challenge. Recent advancements in geno mics, like whole-exome or whole-genome sequencing, have enabled scientists to identify numerous mutations underlying neurodevelopmental disorders. Given the few hundred risk genes that were discovered, the etiological variability and the heterogeneous phenotypic outcomes, the need for genotype -along with phenotype- based diagnosis of individual patients becomes a requisite. Driven by this rationale, in a previous study our group described mutations, identified via whole - exome sequencing, in the gene BCKDK – encoding for a key regulator of branched chain amin o acid (BCAA) catabolism - as a cause of ASD. Following up on the role of BCAAs, in the study described here we show that the solute carrier transporter 7a5 (SLC7A5), a large neutral amino acid transporter localized mainly 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 neurolo gical abnormalities. Additionally, deletion of Slc7a5 from the neural progenitor cell population leads to microcephaly. Interestingly, we demonstrate that BCAA intracerebroventricular administration ameliorates abnormal behaviors in adult mutant mice. Furthermore, whole - exome sequencing of patients diagnosed with neurological dis o r ders helped us identify several patients with autistic traits, microcephaly and motor delay carrying deleterious homozygous mutations in the SLC7A5 gene. In conclusion, our data elucidate a neurological syndrome defined by SLC7A5 mutations and support an essential role for t he BCAA s in human bra in function. Together with r ecent studies (described in chapter two) that have successfully made the transition into clinical practice, our findings on the role of B CAAs might have a crucial impact on the development of novel individualized therapeutic strategies for ASD. ","lang":"eng"}],"month":"03","alternative_title":["ISTA Thesis"]},{"file_date_updated":"2020-07-14T12:44:37Z","department":[{"_id":"GaNo"}],"date_updated":"2024-03-27T23:30:12Z","ddc":["576","616"],"type":"journal_article","article_type":"original","status":"public","pubrep_id":"771","_id":"1183","volume":167,"related_material":{"record":[{"relation":"dissertation_contains","status":"public","id":"395"}]},"issue":"6","publication_status":"published","file":[{"file_name":"IST-2017-771-v1+1_Tarlungeanu_et_al._Final_edited.pdf","date_created":"2018-12-12T10:13:44Z","file_size":73907957,"date_updated":"2020-07-14T12:44:37Z","creator":"system","checksum":"7fe01ab12a6610d3db421e0136db2f77","file_id":"5030","content_type":"application/pdf","relation":"main_file","access_level":"open_access"}],"language":[{"iso":"eng"}],"scopus_import":"1","month":"12","intvolume":" 167","abstract":[{"lang":"eng","text":"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."}],"oa_version":"Submitted Version","author":[{"id":"2ABCE612-F248-11E8-B48F-1D18A9856A87","first_name":"Dora-Clara","full_name":"Tarlungeanu, Dora-Clara","last_name":"Tarlungeanu"},{"full_name":"Deliu, Elena","orcid":"0000-0002-7370-5293","last_name":"Deliu","first_name":"Elena","id":"37A40D7E-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Dotter","orcid":"0000-0002-9033-9096","full_name":"Dotter, Christoph","id":"4C66542E-F248-11E8-B48F-1D18A9856A87","first_name":"Christoph"},{"first_name":"Majdi","last_name":"Kara","full_name":"Kara, Majdi"},{"full_name":"Janiesch, Philipp","last_name":"Janiesch","first_name":"Philipp"},{"first_name":"Mariafrancesca","last_name":"Scalise","full_name":"Scalise, Mariafrancesca"},{"full_name":"Galluccio, Michele","last_name":"Galluccio","first_name":"Michele"},{"first_name":"Mateja","last_name":"Tesulov","full_name":"Tesulov, Mateja"},{"full_name":"Morelli, Emanuela","last_name":"Morelli","id":"3F4D1282-F248-11E8-B48F-1D18A9856A87","first_name":"Emanuela"},{"last_name":"Sönmez","full_name":"Sönmez, Fatma","first_name":"Fatma"},{"first_name":"Kaya","last_name":"Bilgüvar","full_name":"Bilgüvar, Kaya"},{"first_name":"Ryuichi","last_name":"Ohgaki","full_name":"Ohgaki, Ryuichi"},{"first_name":"Yoshikatsu","full_name":"Kanai, Yoshikatsu","last_name":"Kanai"},{"last_name":"Johansen","full_name":"Johansen, Anide","first_name":"Anide"},{"first_name":"Seham","full_name":"Esharif, Seham","last_name":"Esharif"},{"full_name":"Ben Omran, Tawfeg","last_name":"Ben Omran","first_name":"Tawfeg"},{"last_name":"Topcu","full_name":"Topcu, Meral","first_name":"Meral"},{"last_name":"Schlessinger","full_name":"Schlessinger, Avner","first_name":"Avner"},{"first_name":"Cesare","full_name":"Indiveri, Cesare","last_name":"Indiveri"},{"last_name":"Duncan","full_name":"Duncan, Kent","first_name":"Kent"},{"full_name":"Caglayan, Ahmet","last_name":"Caglayan","first_name":"Ahmet"},{"first_name":"Murat","last_name":"Günel","full_name":"Günel, Murat"},{"last_name":"Gleeson","full_name":"Gleeson, Joseph","first_name":"Joseph"},{"last_name":"Novarino","full_name":"Novarino, Gaia","orcid":"0000-0002-7673-7178","first_name":"Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87"}],"publist_id":"6170","article_processing_charge":"No","title":"Impaired amino acid transport at the blood brain barrier is a cause of autism spectrum disorder","citation":{"apa":"Tarlungeanu, D.-C., Deliu, E., Dotter, C., Kara, M., Janiesch, P., Scalise, M., … Novarino, G. (2016). Impaired amino acid transport at the blood brain barrier is a cause of autism spectrum disorder. Cell. Cell Press. https://doi.org/10.1016/j.cell.2016.11.013","ama":"Tarlungeanu D-C, Deliu E, Dotter C, et al. Impaired amino acid transport at the blood brain barrier is a cause of autism spectrum disorder. Cell. 2016;167(6):1481-1494. doi:10.1016/j.cell.2016.11.013","short":"D.-C. Tarlungeanu, E. Deliu, C. Dotter, M. Kara, P. Janiesch, M. Scalise, M. Galluccio, M. Tesulov, E. Morelli, F. Sönmez, K. Bilgüvar, R. Ohgaki, Y. Kanai, A. Johansen, S. Esharif, T. Ben Omran, M. Topcu, A. Schlessinger, C. Indiveri, K. Duncan, A. Caglayan, M. Günel, J. Gleeson, G. Novarino, Cell 167 (2016) 1481–1494.","ieee":"D.-C. Tarlungeanu et al., “Impaired amino acid transport at the blood brain barrier is a cause of autism spectrum disorder,” Cell, vol. 167, no. 6. Cell Press, pp. 1481–1494, 2016.","mla":"Tarlungeanu, Dora-Clara, et al. “Impaired Amino Acid Transport at the Blood Brain Barrier Is a Cause of Autism Spectrum Disorder.” Cell, vol. 167, no. 6, Cell Press, 2016, pp. 1481–94, doi:10.1016/j.cell.2016.11.013.","ista":"Tarlungeanu D-C, Deliu E, Dotter C, Kara M, Janiesch P, Scalise M, Galluccio M, Tesulov M, Morelli E, Sönmez F, Bilgüvar K, Ohgaki R, Kanai Y, Johansen A, Esharif S, Ben Omran T, Topcu M, Schlessinger A, Indiveri C, Duncan K, Caglayan A, Günel M, Gleeson J, Novarino G. 2016. Impaired amino acid transport at the blood brain barrier is a cause of autism spectrum disorder. Cell. 167(6), 1481–1494.","chicago":"Tarlungeanu, Dora-Clara, Elena Deliu, Christoph Dotter, Majdi Kara, Philipp Janiesch, Mariafrancesca Scalise, Michele Galluccio, et al. “Impaired Amino Acid Transport at the Blood Brain Barrier Is a Cause of Autism Spectrum Disorder.” Cell. Cell Press, 2016. https://doi.org/10.1016/j.cell.2016.11.013."},"user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","project":[{"name":"Transmembrane Transporters in Health and Disease","grant_number":"F03523","_id":"25473368-B435-11E9-9278-68D0E5697425","call_identifier":"FWF"}],"page":"1481 - 1494","doi":"10.1016/j.cell.2016.11.013","date_published":"2016-12-01T00:00:00Z","date_created":"2018-12-11T11:50:35Z","has_accepted_license":"1","year":"2016","day":"01","publication":"Cell","quality_controlled":"1","publisher":"Cell Press","oa":1,"acknowledgement":"This work was supported by NICHD (P01HD070494) and SFARI (grant 275275) to J.G.G., and FWF (SFB35_3523) to G.N.\r\nWe thank A.C. Manzano, Mike Liu, and F. Marr for technical assistance, and R. Shigemoto and the IST Austria Electron Microscopy (EM) Facility for assistance. We acknowledge support from CIDR for genome-wide SNP analysis (X01HG008823) and Broad Institute Center for Mendelian Disorders (UM1HG008900 to D. MacArthur), the Yale Center for Mendelian Disorders (U54HG006504 to M.G.), the Gregory M. Kiez and Mehmet Kutman Foundation (M.G.), Italian Ministry of Instruction University and Research (PON01_00937 to C.I.), and NIH (R01-GM108911 to A.S.). This work was supported by NICHD (P01HD070494) and SFARI (grant 275275) to J.G.G., and FWF (SFB35_3523) to G.N.\r\n\r\n#EMFacility"}]