{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T04:09:13Z","timestamp":1785816553759,"version":"3.56.0"},"reference-count":123,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2019,12,9]],"date-time":"2019-12-09T00:00:00Z","timestamp":1575849600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2019,12,9]],"date-time":"2019-12-09T00:00:00Z","timestamp":1575849600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001826","name":"ZonMW Veni","doi-asserted-by":"publisher","award":["91617021"],"award-info":[{"award-number":["91617021"]}],"id":[{"id":"10.13039\/501100001826","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000874","name":"Brain and Behavior Research Foundation","doi-asserted-by":"publisher","award":["NARSAD Young Investigator award"],"award-info":[{"award-number":["NARSAD Young Investigator award"]}],"id":[{"id":"10.13039\/100000874","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Acta Neuropathol"],"published-print":{"date-parts":[[2020,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Developmental and\/or epileptic encephalopathies (DEEs) are a group of devastating genetic disorders, resulting in early-onset, therapy-resistant seizures and developmental delay. Here we report on 22 individuals from 15 families presenting with a severe form of intractable epilepsy, severe developmental delay, progressive microcephaly, visual disturbance and similar minor dysmorphisms. Whole exome sequencing identified a recurrent, homozygous variant (chr2:64083454A\u2009&gt;\u2009G) in the essential\n                    <jats:italic>UDP<\/jats:italic>\n                    -\n                    <jats:italic>glucose pyrophosphorylase<\/jats:italic>\n                    (\n                    <jats:italic>UGP2<\/jats:italic>\n                    ) gene in all probands. This rare variant results in a tolerable Met12Val missense change of the longer UGP2 protein isoform but causes a disruption of the start codon of the shorter isoform, which is predominant in brain. We show that the absence of the shorter isoform leads to a reduction of functional UGP2 enzyme in neural stem cells, leading to altered glycogen metabolism, upregulated unfolded protein response and premature neuronal differentiation, as modeled during pluripotent stem cell differentiation in vitro. In contrast, the complete lack of all UGP2 isoforms leads to differentiation defects in multiple lineages in human cells. Reduced expression of Ugp2a\/Ugp2b in vivo in zebrafish mimics visual disturbance and mutant animals show a behavioral phenotype. Our study identifies a recurrent start codon mutation in\n                    <jats:italic>UGP2<\/jats:italic>\n                    as a cause of a novel autosomal recessive DEE syndrome. Importantly, it also shows that isoform-specific start-loss mutations causing expression loss of a tissue-relevant isoform of an essential protein can cause a genetic disease, even when an organism-wide protein absence is incompatible with life. We provide additional examples where a similar disease mechanism applies.\n                  <\/jats:p>","DOI":"10.1007\/s00401-019-02109-6","type":"journal-article","created":{"date-parts":[[2019,12,9]],"date-time":"2019-12-09T14:04:13Z","timestamp":1575900253000},"page":"415-442","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":64,"title":["Loss of UGP2 in brain leads to a severe epileptic encephalopathy, emphasizing that bi-allelic isoform-specific start-loss mutations of essential genes can cause genetic diseases"],"prefix":"10.1007","volume":"139","author":[{"given":"Elena","family":"Perenthaler","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anita","family":"Nikoncuk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soheil","family":"Yousefi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Woutje M.","family":"Berdowski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maysoon","family":"Alsagob","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan","family":"Capo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Herma C.","family":"van der Linde","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"van den Berg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edwin H.","family":"Jacobs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darija","family":"Putar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehrnaz","family":"Ghazvini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleonora","family":"Aronica","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wilfred F. J.","family":"van IJcken","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walter G.","family":"de Valk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evita","family":"Medici-van den Herik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marjon","family":"van Slegtenhorst","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren","family":"Brick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariya","family":"Kozenko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennefer N.","family":"Kohler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan A.","family":"Bernstein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristin G.","family":"Monaghan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amber","family":"Begtrup","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Torene","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amna","family":"Al Futaisi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fathiya","family":"Al Murshedi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renjith","family":"Mani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faisal","family":"Al Azri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik-Jan","family":"Kamsteeg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Majid","family":"Mojarrad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atieh","family":"Eslahi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zaynab","family":"Khazaei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fateme Massinaei","family":"Darmiyan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad","family":"Doosti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ehsan Ghayoor","family":"Karimiani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jana","family":"Vandrovcova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faisal","family":"Zafar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nuzhat","family":"Rana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krishna K.","family":"Kandaswamy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jozef","family":"Hertecant","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Bauer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed A.","family":"AlMuhaizea","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mustafa A.","family":"Salih","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mazhor","family":"Aldosary","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rawan","family":"Almass","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laila","family":"Al-Quait","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wafa","family":"Qubbaj","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serdar","family":"Coskun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khaled O.","family":"Alahmadi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muddathir H. A.","family":"Hamad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salem","family":"Alwadaee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khalid","family":"Awartani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anas M.","family":"Dababo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Futwan","family":"Almohanna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dilek","family":"Colak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammadreza","family":"Dehghani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad Yahya Vahidi","family":"Mehrjardi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Murat","family":"Gunel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. Gulhan","family":"Ercan-Sencicek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gouri Rao","family":"Passi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huma Arshad","family":"Cheema","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Efthymiou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henry","family":"Houlden","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aida M.","family":"Bertoli-Avella","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice S.","family":"Brooks","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyle","family":"Retterer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reza","family":"Maroofian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Namik","family":"Kaya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tjakko J.","family":"van Ham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1231-1562","authenticated-orcid":false,"given":"Tahsin Stefan","family":"Barakat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,12,9]]},"reference":[{"key":"2109_CR1","unstructured":"(2010) Baluchistan i. Geography, history and ethnography. Encyclop\u00e6dia Iranica City, pp fasc. 6, pp 598\u2013632"},{"key":"2109_CR2","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.bbacli.2016.02.001","volume":"5","author":"MM Adeva-Andany","year":"2016","unstructured":"Adeva-Andany MM, Gonzalez-Lucan M, Donapetry-Garcia C, Fernandez-Fernandez C, Ameneiros-Rodriguez E (2016) Glycogen metabolism in humans. BBA Clin 5:85\u2013100","journal-title":"BBA Clin"},{"key":"2109_CR3","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1093\/bioinformatics\/btu638","volume":"31","author":"S Anders","year":"2015","unstructured":"Anders S, Pyl PT, Huber W (2015) HTSeq\u2013a Python framework to work with high-throughput sequencing data. Bioinformatics 31:166\u2013169","journal-title":"Bioinformatics"},{"key":"2109_CR4","doi-asserted-by":"crossref","first-page":"6164","DOI":"10.1523\/JNEUROSCI.3458-13.2014","volume":"34","author":"AM Arranz","year":"2014","unstructured":"Arranz AM, Perkins KL, Irie F, Lewis DP, Hrabe J, Xiao F et al (2014) Hyaluronan deficiency due to Has3 knock-out causes altered neuronal activity and seizures via reduction in brain extracellular space. J Neurosci 34:6164\u20136176","journal-title":"J Neurosci"},{"key":"2109_CR5","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1186\/s12885-019-5455-1","volume":"19","author":"J Bakke","year":"2019","unstructured":"Bakke J, Wright WC, Zamora AE, Oladimeji P, Crawford JC, Brewer CT et al (2019) Genome-wide CRISPR screen reveals PSMA6 to be an essential gene in pancreatic cancer cells. BMC Cancer 19:253","journal-title":"BMC Cancer"},{"key":"2109_CR6","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/j.stemcr.2014.12.012","volume":"4","author":"TS Barakat","year":"2015","unstructured":"Barakat TS, Ghazvini M, de Hoon B, Li T, Eussen B, Douben H et al (2015) Stable X chromosome reactivation in female human induced pluripotent stem cells. Stem Cell Rep 4:199\u2013208","journal-title":"Stem Cell Rep"},{"key":"2109_CR7","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1007\/978-1-4939-1652-8_7","volume":"1227","author":"TS Barakat","year":"2015","unstructured":"Barakat TS, Gribnau J (2015) Generation of knockout alleles by RFLP based BAC targeting of polymorphic embryonic stem cells. Methods Mol Biol 1227:143\u2013180","journal-title":"Methods Mol Biol"},{"key":"2109_CR8","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1007\/978-1-4419-7037-4_10","volume":"695","author":"TS Barakat","year":"2010","unstructured":"Barakat TS, Gribnau J (2010) X chromosome inactivation and embryonic stem cells. Adv Exp Med Biol 695:132\u2013154","journal-title":"Adv Exp Med Biol"},{"issue":"276\u2013288","key":"2109_CR9","first-page":"e278","volume":"23","author":"TS Barakat","year":"2018","unstructured":"Barakat TS, Halbritter F, Zhang M, Rendeiro AF, Perenthaler E, Bock C et al (2018) Functional dissection of the enhancer repertoire in human embryonic stem cells. Cell Stem Cell 23(276\u2013288):e278","journal-title":"Cell Stem Cell"},{"key":"2109_CR10","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1038\/nrg.2017.75","volume":"19","author":"I Bartha","year":"2018","unstructured":"Bartha I, di Iulio J, Venter JC, Telenti A (2018) Human gene essentiality. Nat Rev Genet 19:51\u201362","journal-title":"Nat Rev Genet"},{"key":"2109_CR11","volume-title":"Atlas of human central nervous system development: the human brain during the third trimester","author":"SA Bayer","year":"2004","unstructured":"Bayer SA, Altman J (2004) Atlas of human central nervous system development: the human brain during the third trimester, vol 2. CRC Press, New York"},{"key":"2109_CR12","doi-asserted-by":"crossref","DOI":"10.1201\/9780203507483","volume-title":"Atlas of human central nervous system development: the human brain during the second trimester","author":"SA Bayer","year":"2005","unstructured":"Bayer SA, Altman J (2005) Atlas of human central nervous system development: the human brain during the second trimester, vol 3. CRC Press, New York"},{"key":"2109_CR13","doi-asserted-by":"crossref","DOI":"10.1201\/9781420003277","volume-title":"Atlas of human central nervous system development: the human brain during the late first trimester","author":"SA Bayer","year":"2006","unstructured":"Bayer SA, Altman J (2006) Atlas of human central nervous system development: the human brain during the late first trimester, vol 4. CRC Press, New York"},{"key":"2109_CR14","volume-title":"Atlas of human central nervous system development: the human brain during the early first trimester","author":"SA Bayer","year":"2008","unstructured":"Bayer SA, Altman J (2008) Atlas of human central nervous system development: the human brain during the early first trimester, vol 5. CRC Press, New York"},{"key":"2109_CR15","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1128\/MCB.00302-17","volume":"38","author":"T Bertomeu","year":"2018","unstructured":"Bertomeu T, Coulombe-Huntington J, Chatr-Aryamontri A, Bourdages KG, Coyaud E, Raught B et al (2018) A high-resolution genome-wide CRISPR\/Cas9 viability screen reveals structural features and contextual diversity of the human cell-essential proteome. Mol Cell Biol 38:10","journal-title":"Mol Cell Biol"},{"key":"2109_CR16","doi-asserted-by":"crossref","first-page":"1814","DOI":"10.1093\/brain\/awg174","volume":"126","author":"J Binder","year":"2003","unstructured":"Binder J, Hofmann S, Kreisel S, Wohrle JC, Bazner H, Krauss JK et al (2003) Clinical and molecular findings in a patient with a novel mutation in the deafness-dystonia peptide (DDP1) gene. Brain 126:1814\u20131820","journal-title":"Brain"},{"key":"2109_CR17","doi-asserted-by":"crossref","first-page":"1092","DOI":"10.1126\/science.aac7557","volume":"350","author":"VA Blomen","year":"2015","unstructured":"Blomen VA, Majek P, Jae LT, Bigenzahn JW, Nieuwenhuis J, Staring J et al (2015) Gene essentiality and synthetic lethality in haploid human cells. Science 350:1092\u20131096","journal-title":"Science"},{"key":"2109_CR18","doi-asserted-by":"crossref","first-page":"e168","DOI":"10.1093\/nar\/gku936","volume":"42","author":"EK Brinkman","year":"2014","unstructured":"Brinkman EK, Chen T, Amendola M, van Steensel B (2014) Easy quantitative assessment of genome editing by sequence trace decomposition. Nucleic Acids Res 42:e168","journal-title":"Nucleic Acids Res"},{"key":"2109_CR19","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1111\/eci.12019","volume":"43","author":"G Caridi","year":"2013","unstructured":"Caridi G, Dagnino M, Lugani F, Shalev SA, Campagnoli M, Galliano M et al (2013) A novel mutation in the albumin gene (c.1A %3e C) resulting in analbuminemia. Eur J Clin Invest 43:72\u201378","journal-title":"Eur J Clin Invest"},{"key":"2109_CR20","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1038\/nbt.1529","volume":"27","author":"SM Chambers","year":"2009","unstructured":"Chambers SM, Fasano CA, Papapetrou EP, Tomishima M, Sadelain M, Studer L (2009) Highly efficient neural conversion of human ES and iPS cells by dual inhibition of SMAD signaling. Nat Biotechnol 27:275\u2013280","journal-title":"Nat Biotechnol"},{"key":"2109_CR21","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1105\/tpc.106.044123","volume":"19","author":"R Chen","year":"2007","unstructured":"Chen R, Zhao X, Shao Z, Wei Z, Wang Y, Zhu L et al (2007) Rice UDP-glucose pyrophosphorylase1 is essential for pollen callose deposition and its cosuppression results in a new type of thermosensitive genic male sterility. Plant Cell 19:847\u2013861","journal-title":"Plant Cell"},{"key":"2109_CR22","doi-asserted-by":"crossref","first-page":"1094","DOI":"10.1016\/j.neuron.2012.08.032","volume":"75","author":"HB Choi","year":"2012","unstructured":"Choi HB, Gordon GR, Zhou N, Tai C, Rungta RL, Martinez J et al (2012) Metabolic communication between astrocytes and neurons via bicarbonate-responsive soluble adenylyl cyclase. Neuron 75:1094\u20131104","journal-title":"Neuron"},{"key":"2109_CR23","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1038\/ng.2653","volume":"45","author":"Consortium GT","year":"2013","unstructured":"Consortium GT (2013) The genotype-tissue expression (GTEx) project. Nat Genet 45:580\u2013585","journal-title":"Nat Genet"},{"issue":"5","key":"2109_CR24","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1016\/j.stem.2019.03.023","volume":"24","author":"EC Cope","year":"2019","unstructured":"Cope EC, Gould E (2019) Adult Neurogenesis, glia, and the extracellular matrix. Cell Stem Cell 24(5):690\u2013705","journal-title":"Cell Stem Cell"},{"key":"2109_CR25","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1111\/j.1574-6968.1997.tb10468.x","volume":"153","author":"JM Daran","year":"1997","unstructured":"Daran JM, Bell W, Francois J (1997) Physiological and morphological effects of genetic alterations leading to a reduced synthesis of UDP-glucose in Saccharomyces cerevisiae. FEMS Microbiol Lett 153:89\u201396","journal-title":"FEMS Microbiol Lett"},{"key":"2109_CR26","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1111\/j.1432-1033.1995.520_2.x","volume":"233","author":"JM Daran","year":"1995","unstructured":"Daran JM, Dallies N, Thines-Sempoux D, Paquet V, Francois J (1995) Genetic and biochemical characterization of the UGP1 gene encoding the UDP-glucose pyrophosphorylase from Saccharomyces cerevisiae. Eur J Biochem 233:520\u2013530","journal-title":"Eur J Biochem"},{"key":"2109_CR27","doi-asserted-by":"crossref","first-page":"1825","DOI":"10.1038\/leu.2011.172","volume":"25","author":"HJ de Jonge","year":"2011","unstructured":"de Jonge HJ, Woolthuis CM, Vos AZ, Mulder A, van den Berg E, Kluin PM et al (2011) Gene expression profiling in the leukemic stem cell-enriched CD34 + fraction identifies target genes that predict prognosis in normal karyotype AML. Leukemia 25:1825\u20131833","journal-title":"Leukemia"},{"key":"2109_CR28","doi-asserted-by":"crossref","first-page":"2843","DOI":"10.1084\/jem.20130751","volume":"210","author":"E de Pater","year":"2013","unstructured":"de Pater E, Kaimakis P, Vink CS, Yokomizo T, Yamada-Inagawa T, van der Linden R et al (2013) Gata2 is required for HSC generation and survival. J Exp Med 210:2843\u20132850","journal-title":"J Exp Med"},{"key":"2109_CR29","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.gep.2015.05.004","volume":"19","author":"N Diotel","year":"2015","unstructured":"Diotel N, Beil T, Strahle U, Rastegar S (2015) Differential expression of id genes and their potential regulator znf238 in zebrafish adult neural progenitor cells and neurons suggests distinct functions in adult neurogenesis. Gene Expr Patterns 19:1\u201313","journal-title":"Gene Expr Patterns"},{"key":"2109_CR30","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1038\/jcbfm.2012.200","volume":"33","author":"J Duran","year":"2013","unstructured":"Duran J, Saez I, Gruart A, Guinovart JJ, Delgado-Garcia JM (2013) Impairment in long-term memory formation and learning-dependent synaptic plasticity in mice lacking glycogen synthase in the brain. J Cereb Blood Flow Metab 33:550\u2013556","journal-title":"J Cereb Blood Flow Metab"},{"key":"2109_CR31","first-page":"4","volume":"1","author":"Epi25 Collaborative, Electronic address sbuea, Epi C","year":"2019","unstructured":"Epi25 Collaborative, Electronic address sbuea, Epi C (2019) Ultra-rare genetic variation in the epilepsies: a whole-exome sequencing study of 17,606 individuals. Am J Hum Genet 1:4","journal-title":"Am J Hum Genet"},{"key":"2109_CR32","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1038\/nature12439","volume":"501","author":"KC Epi","year":"2013","unstructured":"Epi KC, Phenome E, Genome P, Allen AS, Berkovic SF, Cossette P, Delanty N et al (2013) De novo mutations in epileptic encephalopathies. Nature 501:217\u2013221","journal-title":"Nature"},{"key":"2109_CR33","unstructured":"Exome Variant Server NHLBI GO Exome Sequencing Project (ESP) Seattle WA (accessed Juli 2019)."},{"key":"2109_CR34","first-page":"4","volume":"1","author":"Z Fattahi","year":"2019","unstructured":"Fattahi Z, Beheshtian M, Mohseni M, Poustchi H, Sellars E, Nezhadi SH et al (2019) Iranome: a catalog of genomic variations in the Iranian population. Hum Mutat 1:4","journal-title":"Hum Mutat"},{"key":"2109_CR35","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1016\/j.ajhg.2009.03.010","volume":"84","author":"HV Firth","year":"2009","unstructured":"Firth HV, Richards SM, Bevan AP, Clayton S, Corpas M, Rajan D et al (2009) DECIPHER: database of chromosomal imbalance and phenotype in humans using Ensembl resources. Am J Hum Genet 84:524\u2013533","journal-title":"Am J Hum Genet"},{"key":"2109_CR36","doi-asserted-by":"crossref","first-page":"23784","DOI":"10.1074\/jbc.272.38.23784","volume":"272","author":"M Flores-Diaz","year":"1997","unstructured":"Flores-Diaz M, Alape-Giron A, Persson B, Pollesello P, Moos M, von Eichel-Streiber C et al (1997) Cellular UDP-glucose deficiency caused by a single point mutation in the UDP-glucose pyrophosphorylase gene. J Biol Chem 272:23784\u201323791","journal-title":"J Biol Chem"},{"key":"2109_CR37","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1002\/humu.21438","volume":"32","author":"IF Fokkema","year":"2011","unstructured":"Fokkema IF, Taschner PE, Schaafsma GC, Celli J, Laros JF, den Dunnen JT (2011) LOVD vol 2.0: the next generation in gene variant databases. Hum Mutat 32:557\u2013563","journal-title":"Hum Mutat"},{"key":"2109_CR38","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1093\/glycob\/cws217","volume":"23","author":"J Fuhring","year":"2013","unstructured":"Fuhring J, Damerow S, Fedorov R, Schneider J, Munster-Kuhnel AK, Gerardy-Schahn R (2013) Octamerization is essential for enzymatic function of human UDP-glucose pyrophosphorylase. Glycobiology 23:426\u2013437","journal-title":"Glycobiology"},{"key":"2109_CR39","doi-asserted-by":"crossref","first-page":"9618","DOI":"10.1038\/srep09618","volume":"5","author":"JI Fuhring","year":"2015","unstructured":"Fuhring JI, Cramer JT, Schneider J, Baruch P, Gerardy-Schahn R, Fedorov R (2015) A quaternary mechanism enables the complex biological functions of octameric human UDP-glucose pyrophosphorylase, a key enzyme in cell metabolism. Sci Rep 5:9618","journal-title":"Sci Rep"},{"key":"2109_CR40","doi-asserted-by":"crossref","first-page":"950","DOI":"10.1002\/humu.22836","volume":"36","author":"M Gonzalez","year":"2015","unstructured":"Gonzalez M, Falk MJ, Gai X, Postrel R, Schule R, Zuchner S (2015) Innovative genomic collaboration using the GENESIS (GEM.app) platform. Hum Mutat 36:950\u2013956","journal-title":"Hum Mutat"},{"key":"2109_CR41","doi-asserted-by":"crossref","first-page":"3155","DOI":"10.1093\/hmg\/ddv066","volume":"24","author":"KB Gostynska","year":"2015","unstructured":"Gostynska KB, Nijenhuis M, Lemmink H, Pas HH, Pasmooij AM, Lang KK et al (2015) Mutation in exon 1a of PLEC, leading to disruption of plectin isoform 1a, causes autosomal-recessive skin-only epidermolysis bullosa simplex. Hum Mol Genet 24:3155\u20133162","journal-title":"Hum Mol Genet"},{"key":"2109_CR42","doi-asserted-by":"crossref","first-page":"4123","DOI":"10.1074\/jbc.M116.763201","volume":"292","author":"H Guo","year":"2017","unstructured":"Guo H, Zhang B, Nairn AV, Nagy T, Moremen KW, Buckhaults P et al (2017) O-Linked N-acetylglucosamine (O-GlcNAc) expression levels epigenetically regulate colon cancer tumorigenesis by affecting the cancer stem cell compartment via modulating expression of transcriptional factor MYBL1. J Biol Chem 292:4123\u20134137","journal-title":"J Biol Chem"},{"key":"2109_CR43","doi-asserted-by":"crossref","first-page":"1515","DOI":"10.1016\/j.cell.2015.11.015","volume":"163","author":"T Hart","year":"2015","unstructured":"Hart T, Chandrashekhar M, Aregger M, Steinhart Z, Brown KR, MacLeod G et al (2015) High-resolution CRISPR screens reveal fitness genes and genotype-specific cancer liabilities. Cell 163:1515\u20131526","journal-title":"Cell"},{"key":"2109_CR44","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1042\/bj20021320","volume":"370","author":"JC Higuita","year":"2003","unstructured":"Higuita JC, Alape-Giron A, Thelestam M, Katz A (2003) A point mutation in the UDP-glucose pyrophosphorylase gene results in decreases of UDP-glucose and inactivation of glycogen synthase. Biochem J 370:995\u20131001","journal-title":"Biochem J"},{"key":"2109_CR45","first-page":"6307","volume":"16","author":"S Hua","year":"2018","unstructured":"Hua S, Li H, Liu Y, Zhang J, Cheng Y, Dai C (2018) High expression of GALNT7 promotes invasion and proliferation of glioma cells. Oncol Lett 16:6307\u20136314","journal-title":"Oncol Lett"},{"key":"2109_CR46","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1038\/nn.4337","volume":"19","author":"T Hwang","year":"2016","unstructured":"Hwang T, Park CK, Leung AK, Gao Y, Hyde TM, Kleinman JE et al (2016) Dynamic regulation of RNA editing in human brain development and disease. Nat Neurosci 19:1093\u20131099","journal-title":"Nat Neurosci"},{"key":"2109_CR47","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1002\/humu.23355","volume":"39","author":"ZA Jenkins","year":"2018","unstructured":"Jenkins ZA, Macharg A, Chang CY, van Kogelenberg M, Morgan T, Frentz S et al (2018) Differential regulation of two FLNA transcripts explains some of the phenotypic heterogeneity in the loss-of-function filaminopathies. Hum Mutat 39:103\u2013113","journal-title":"Hum Mutat"},{"key":"2109_CR48","doi-asserted-by":"crossref","first-page":"3699","DOI":"10.1093\/hmg\/ddw217","volume":"25","author":"PP Jumbo-Lucioni","year":"2016","unstructured":"Jumbo-Lucioni PP, Parkinson WM, Kopke DL, Broadie K (2016) Coordinated movement, neuromuscular synaptogenesis and trans-synaptic signaling defects in Drosophila galactosemia models. Hum Mol Genet 25:3699\u20133714","journal-title":"Hum Mol Genet"},{"key":"2109_CR49","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1097\/WCO.0000000000000535","volume":"31","author":"J Kalser","year":"2018","unstructured":"Kalser J, Cross JH (2018) The epileptic encephalopathy jungle\u2014from Dr West to the concepts of aetiology-related and developmental encephalopathies. Curr Opin Neurol 31:216\u2013222","journal-title":"Curr Opin Neurol"},{"key":"2109_CR50","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1038\/nmeth.3317","volume":"12","author":"D Kim","year":"2015","unstructured":"Kim D, Langmead B, Salzberg SL (2015) HISAT: a fast spliced aligner with low memory requirements. Nat Methods 12:357\u2013360","journal-title":"Nat Methods"},{"key":"2109_CR51","doi-asserted-by":"crossref","first-page":"1705","DOI":"10.1002\/glia.23641","volume":"67","author":"LE Kuil","year":"2019","unstructured":"Kuil LE, Lopez Marti A, Carreras Mascaro A, van den Bosch JC, van den Berg P, van der Linde HC et al (2019) Hexb enzyme deficiency leads to lysosomal abnormalities in radial glia and microglia in zebrafish brain development. Glia 67:1705\u20131718","journal-title":"Glia"},{"key":"2109_CR52","doi-asserted-by":"crossref","first-page":"W90","DOI":"10.1093\/nar\/gkw377","volume":"44","author":"MV Kuleshov","year":"2016","unstructured":"Kuleshov MV, Jones MR, Rouillard AD, Fernandez NF, Duan Q, Wang Z et al (2016) Enrichr: a comprehensive gene set enrichment analysis web server 2016 update. Nucleic Acids Res 44:W90\u201397","journal-title":"Nucleic Acids Res"},{"key":"2109_CR53","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.eplepsyres.2019.02.009","volume":"151","author":"J Kyyriainen","year":"2019","unstructured":"Kyyriainen J, Bolkvadze T, Koivisto H, Lipponen A, Perez LO, Ekolle Ndode-Ekane X et al (2019) Deficiency of urokinase-type plasminogen activator and its receptor affects social behavior and increases seizure susceptibility. Epilepsy Res 151:67\u201374","journal-title":"Epilepsy Res"},{"key":"2109_CR54","doi-asserted-by":"crossref","first-page":"D980","DOI":"10.1093\/nar\/gkt1113","volume":"42","author":"MJ Landrum","year":"2014","unstructured":"Landrum MJ, Lee JM, Riley GR, Jang W, Rubinstein WS, Church DM et al (2014) ClinVar: public archive of relationships among sequence variation and human phenotype. Nucleic Acids Res 42:D980\u2013985","journal-title":"Nucleic Acids Res"},{"key":"2109_CR55","doi-asserted-by":"crossref","first-page":"e1003118","DOI":"10.1371\/journal.pcbi.1003118","volume":"9","author":"M Lawrence","year":"2013","unstructured":"Lawrence M, Huber W, Pages H, Aboyoun P, Carlson M, Gentleman R et al (2013) Software for computing and annotating genomic ranges. PLoS Comput Biol 9:e1003118","journal-title":"PLoS Comput Biol"},{"key":"2109_CR56","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1038\/nature19057","volume":"536","author":"M Lek","year":"2016","unstructured":"Lek M, Karczewski KJ, Minikel EV, Samocha KE, Banks E, Fennell T et al (2016) Analysis of protein-coding genetic variation in 60,706 humans. Nature 536:285\u2013291","journal-title":"Nature"},{"key":"2109_CR57","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1016\/j.ajhg.2016.03.001","volume":"98","author":"J Li","year":"2016","unstructured":"Li J, Woods SL, Healey S, Beesley J, Chen X, Lee JS et al (2016) Point mutations in exon 1B of APC reveal gastric adenocarcinoma and proximal polyposis of the stomach as a familial adenomatous polyposis variant. Am J Hum Genet 98:830\u2013842","journal-title":"Am J Hum Genet"},{"key":"2109_CR58","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/j.fgb.2015.07.012","volume":"82","author":"M Li","year":"2015","unstructured":"Li M, Chen T, Gao T, Miao Z, Jiang A, Shi L et al (2015) UDP-glucose pyrophosphorylase influences polysaccharide synthesis, cell wall components, and hyphal branching in Ganoderma lucidum via regulation of the balance between glucose-1-phosphate and UDP-glucose. Fungal Genet Biol 82:251\u2013263","journal-title":"Fungal Genet Biol"},{"key":"2109_CR59","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1002\/hep.30158","volume":"69","author":"S Li","year":"2019","unstructured":"Li S, Hu Z, Zhao Y, Huang S, He X (2019) Transcriptome-wide analysis reveals the landscape of aberrant alternative splicing events in liver cancer. Hepatology 69:359\u2013375","journal-title":"Hepatology"},{"key":"2109_CR60","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.gene.2018.03.032","volume":"659","author":"Y Li","year":"2018","unstructured":"Li Y, Sun S, Ding Z, Yang C, Zhang G, Jiang Q et al (2018) Temporal and spatial expression of fgfbp genes in zebrafish. Gene 659:128\u2013136","journal-title":"Gene"},{"key":"2109_CR61","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1074\/mcp.RA118.000586","volume":"17","author":"Y Li","year":"2018","unstructured":"Li Y, Zhuang H, Zhang X, Li Y, Liu Y, Yi X et al (2018) Multiomics integration reveals the landscape of prometastasis metabolism in hepatocellular carcinoma. Mol Cell Proteom 17:607\u2013618","journal-title":"Mol Cell Proteom"},{"key":"2109_CR62","doi-asserted-by":"crossref","first-page":"980","DOI":"10.1016\/j.cca.2010.03.032","volume":"411","author":"M Lindhout","year":"2010","unstructured":"Lindhout M, Rubio-Gozalbo ME, Bakker JA, Bierau J (2010) Direct non-radioactive assay of galactose-1-phosphate:uridyltransferase activity using high performance liquid chromatography. Clin Chim Acta 411:980\u2013983","journal-title":"Clin Chim Acta"},{"key":"2109_CR63","first-page":"431","volume":"9","author":"JC Lopez-Ramos","year":"2015","unstructured":"Lopez-Ramos JC, Duran J, Gruart A, Guinovart JJ, Delgado-Garcia JM (2015) Role of brain glycogen in the response to hypoxia and in susceptibility to epilepsy. Front Cell Neurosci 9:431","journal-title":"Front Cell Neurosci"},{"key":"2109_CR64","doi-asserted-by":"crossref","first-page":"46543","DOI":"10.1038\/srep46543","volume":"7","author":"S Lugert","year":"2017","unstructured":"Lugert S, Kremer T, Jagasia R, Herrmann A, Aigner S, Giachino C et al (2017) Glypican-2 levels in cerebrospinal fluid predict the status of adult hippocampal neurogenesis. Sci Rep 7:46543","journal-title":"Sci Rep"},{"key":"2109_CR65","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1042\/bj3600667","volume":"360","author":"C Magee","year":"2001","unstructured":"Magee C, Nurminskaya M, Linsenmayer TF (2001) UDP-glucose pyrophosphorylase: up-regulation in hypertrophic cartilage and role in hyaluronan synthesis. Biochem J 360:667\u2013674","journal-title":"Biochem J"},{"issue":"2","key":"2109_CR66","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1016\/j.celrep.2019.02.041","volume":"27","author":"B Mair","year":"2019","unstructured":"Mair B, Tomic J, Masud SN, Tonge P, Weiss A, Usaj M et al (2019) Essential gene profiles for human pluripotent stem cells identify uncharacterized genes and substrate dependencies. Cell Rep 27(2):599\u2013615.e12","journal-title":"Cell Rep"},{"key":"2109_CR67","doi-asserted-by":"crossref","first-page":"1297","DOI":"10.1101\/gr.107524.110","volume":"20","author":"A McKenna","year":"2010","unstructured":"McKenna A, Hanna M, Banks E, Sivachenko A, Cibulskis K, Kernytsky A et al (2010) The genome analysis toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data. Genome Res 20:1297\u20131303","journal-title":"Genome Res"},{"key":"2109_CR68","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1016\/S1474-4422(15)00250-1","volume":"15","author":"A McTague","year":"2016","unstructured":"McTague A, Howell KB, Cross JH, Kurian MA, Scheffer IE (2016) The genetic landscape of the epileptic encephalopathies of infancy and childhood. Lancet Neurol 15:304\u2013316","journal-title":"Lancet Neurol"},{"key":"2109_CR69","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1016\/j.ajhg.2016.02.015","volume":"98","author":"NE Mencacci","year":"2016","unstructured":"Mencacci NE, Kamsteeg EJ, Nakashima K, R'Bibo L, Lynch DS, Balint B et al (2016) De novo mutations in PDE10A cause childhood-onset chorea with bilateral striatal lesions. Am J Hum Genet 98:763\u2013771","journal-title":"Am J Hum Genet"},{"key":"2109_CR70","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1126\/science.aac8624","volume":"352","author":"VM Narasimhan","year":"2016","unstructured":"Narasimhan VM, Hunt KA, Mason D, Baker CL, Karczewski KJ, Barnes MR et al (2016) Health and population effects of rare gene knockouts in adult humans with related parents. Science 352:474\u2013477","journal-title":"Science"},{"key":"2109_CR71","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/j.seizure.2019.04.018","volume":"69","author":"M Nashabat","year":"2019","unstructured":"Nashabat M, Al Qahtani XS, Almakdob S, Altwaijri W, Ba-Armah DM, Hundallah K et al (2019) The landscape of early infantile epileptic encephalopathy in a consanguineous population. Seizure 69:154\u2013172","journal-title":"Seizure"},{"key":"2109_CR72","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.scr.2015.12.011","volume":"16","author":"LE Oikari","year":"2016","unstructured":"Oikari LE, Okolicsanyi RK, Qin A, Yu C, Griffiths LR, Haupt LM (2016) Cell surface heparan sulfate proteoglycans as novel markers of human neural stem cell fate determination. Stem Cell Res 16:92\u2013104","journal-title":"Stem Cell Res"},{"key":"2109_CR73","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.braindev.2016.07.004","volume":"39","author":"T Okazaki","year":"2017","unstructured":"Okazaki T, Saito Y, Ueda R, Awashima T, Nishimura Y, Yuasa I et al (2017) Epileptic phenotype of FGFR3-related bilateral medial temporal lobe dysgenesis. Brain Dev 39:67\u201371","journal-title":"Brain Dev"},{"key":"2109_CR74","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1038\/s41431-018-0299-8","volume":"27","author":"SM Papuc","year":"2019","unstructured":"Papuc SM, Abela L, Steindl K, Begemann A, Simmons TL, Schmitt B et al (2019) The role of recessive inheritance in early-onset epileptic encephalopathies: a combined whole-exome sequencing and copy number study. Eur J Hum Genet 27:408\u2013421","journal-title":"Eur J Hum Genet"},{"key":"2109_CR75","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1093\/pcp\/pcq057","volume":"51","author":"JI Park","year":"2010","unstructured":"Park JI, Ishimizu T, Suwabe K, Sudo K, Masuko H, Hakozaki H et al (2010) UDP-glucose pyrophosphorylase is rate limiting in vegetative and reproductive phases in Arabidopsis thaliana. Plant Cell Physiol 51:981\u2013996","journal-title":"Plant Cell Physiol"},{"key":"2109_CR76","doi-asserted-by":"crossref","first-page":"352","DOI":"10.3389\/fncel.2019.00352","volume":"13","author":"E Perenthaler","year":"2019","unstructured":"Perenthaler E, Yousefi S, Niggl E, Barakat TS (2019) Beyond the exome: the non-coding genome and enhancers in neurodevelopmental disorders and malformations of cortical development. Front Cell Neurosci 13:352","journal-title":"Front Cell Neurosci"},{"key":"2109_CR77","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1515\/revneuro-2017-0017","volume":"28","author":"KL Perkins","year":"2017","unstructured":"Perkins KL, Arranz AM, Yamaguchi Y, Hrabetova S (2017) Brain extracellular space, hyaluronan, and the prevention of epileptic seizures. Rev Neurosci 28:869\u2013892","journal-title":"Rev Neurosci"},{"key":"2109_CR78","doi-asserted-by":"crossref","first-page":"e9644","DOI":"10.1371\/journal.pone.0009644","volume":"5","author":"N Pescador","year":"2010","unstructured":"Pescador N, Villar D, Cifuentes D, Garcia-Rocha M, Ortiz-Barahona A, Vazquez S et al (2010) Hypoxia promotes glycogen accumulation through hypoxia inducible factor (HIF)-mediated induction of glycogen synthase 1. PLoS ONE 5:e9644","journal-title":"PLoS ONE"},{"key":"2109_CR79","doi-asserted-by":"crossref","first-page":"W191","DOI":"10.1093\/nar\/gkz369","volume":"47","author":"U Raudvere","year":"2019","unstructured":"Raudvere U, Kolberg L, Kuzmin I, Arak T, Adler P, Peterson H et al (2019) g:Profiler: a web server for functional enrichment analysis and conversions of gene lists (2019 update). Nucleic Acids Res 47:W191\u2013W198","journal-title":"Nucleic Acids Res"},{"key":"2109_CR80","doi-asserted-by":"crossref","first-page":"2263","DOI":"10.1016\/j.celrep.2016.02.018","volume":"14","author":"JB Renaud","year":"2016","unstructured":"Renaud JB, Boix C, Charpentier M, De Cian A, Cochennec J, Duvernois-Berthet E et al (2016) Improved genome editing efficiency and flexibility using modified oligonucleotides with TALEN and CRISPR-Cas9 nucleases. Cell Rep 14:2263\u20132272","journal-title":"Cell Rep"},{"key":"2109_CR81","doi-asserted-by":"crossref","first-page":"D886","DOI":"10.1093\/nar\/gky1016","volume":"47","author":"P Rentzsch","year":"2019","unstructured":"Rentzsch P, Witten D, Cooper GM, Shendure J, Kircher M (2019) CADD: predicting the deleteriousness of variants throughout the human genome. Nucleic Acids Res 47:D886\u2013D894","journal-title":"Nucleic Acids Res"},{"key":"2109_CR82","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1038\/gim.2015.148","volume":"18","author":"K Retterer","year":"2016","unstructured":"Retterer K, Juusola J, Cho MT, Vitazka P, Millan F, Gibellini F et al (2016) Clinical application of whole-exome sequencing across clinical indications. Genet Med 18:696\u2013704","journal-title":"Genet Med"},{"key":"2109_CR83","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1038\/nature14248","volume":"518","author":"C Roadmap Epigenomics","year":"2015","unstructured":"Roadmap Epigenomics C, Kundaje A, Meuleman W, Ernst J, Bilenky M, Yen A et al (2015) Integrative analysis of 111 reference human epigenomes. Nature 518:317\u2013330","journal-title":"Nature"},{"key":"2109_CR84","doi-asserted-by":"crossref","first-page":"1539","DOI":"10.1007\/s10815-019-01499-6","volume":"36","author":"SM Robbins","year":"2019","unstructured":"Robbins SM, Thimm MA, Valle D, Jelin AC (2019) Genetic diagnosis in first or second trimester pregnancy loss using exome sequencing: a systematic review of human essential genes. J Assist Reprod Genet 36:1539\u20131548","journal-title":"J Assist Reprod Genet"},{"key":"2109_CR85","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1093\/bioinformatics\/btp616","volume":"26","author":"MD Robinson","year":"2010","unstructured":"Robinson MD, McCarthy DJ, Smyth GK (2010) edgeR: a bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics 26:139\u2013140","journal-title":"Bioinformatics"},{"key":"2109_CR86","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1038\/nature22034","volume":"544","author":"D Saleheen","year":"2017","unstructured":"Saleheen D, Natarajan P, Armean IM, Zhao W, Rasheed A, Khetarpal SA et al (2017) Human knockouts and phenotypic analysis in a cohort with a high rate of consanguinity. Nature 544:235\u2013239","journal-title":"Nature"},{"key":"2109_CR87","doi-asserted-by":"crossref","first-page":"e26049","DOI":"10.1371\/journal.pone.0026049","volume":"6","author":"D Salyakina","year":"2011","unstructured":"Salyakina D, Cukier HN, Lee JM, Sacharow S, Nations LD, Ma D et al (2011) Copy number variants in extended autism spectrum disorder families reveal candidates potentially involved in autism risk. PLoS ONE 6:e26049","journal-title":"PLoS ONE"},{"key":"2109_CR88","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1007\/s12640-010-9171-5","volume":"18","author":"A Schousboe","year":"2010","unstructured":"Schousboe A, Sickmann HM, Walls AB, Bak LK, Waagepetersen HS (2010) Functional importance of the astrocytic glycogen-shunt and glycolysis for maintenance of an intact intra\/extracellular glutamate gradient. Neurotox Res 18:94\u201399","journal-title":"Neurotox Res"},{"key":"2109_CR89","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1038\/nmeth.2890","volume":"11","author":"JM Schwarz","year":"2014","unstructured":"Schwarz JM, Cooper DN, Schuelke M, Seelow D (2014) MutationTaster2: mutation prediction for the deep-sequencing age. Nat Methods 11:361\u2013362","journal-title":"Nat Methods"},{"key":"2109_CR90","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1038\/ng.3592","volume":"48","author":"EM Scott","year":"2016","unstructured":"Scott EM, Halees A, Itan Y, Spencer EG, He Y, Azab MA et al (2016) Characterization of Greater Middle Eastern genetic variation for enhanced disease gene discovery. Nat Genet 48:1071\u20131076","journal-title":"Nat Genet"},{"key":"2109_CR91","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.gep.2016.12.002","volume":"23\u201324","author":"S Sel","year":"2017","unstructured":"Sel S, Patzel E, Poggi L, Kaiser D, Kalinski T, Schicht M et al (2017) Temporal and spatial expression pattern of Nnat during mouse eye development. Gene Express Patterns 23\u201324:7\u201312","journal-title":"Gene Express Patterns"},{"key":"2109_CR92","doi-asserted-by":"crossref","first-page":"9482","DOI":"10.1074\/jbc.M112.416180","volume":"288","author":"J Sharma","year":"2013","unstructured":"Sharma J, Mukherjee D, Rao SN, Iyengar S, Shankar SK, Satishchandra P et al (2013) Neuronatin-mediated aberrant calcium signaling and endoplasmic reticulum stress underlie neuropathology in Lafora disease. J Biol Chem 288:9482\u20139490","journal-title":"J Biol Chem"},{"key":"2109_CR93","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.nbd.2011.06.013","volume":"44","author":"J Sharma","year":"2011","unstructured":"Sharma J, Rao SN, Shankar SK, Satishchandra P, Jana NR (2011) Lafora disease ubiquitin ligase malin promotes proteasomal degradation of neuronatin and regulates glycogen synthesis. Neurobiol Dis 44:133\u2013141","journal-title":"Neurobiol Dis"},{"key":"2109_CR94","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1016\/j.celrep.2015.08.082","volume":"13","author":"HP Shih","year":"2015","unstructured":"Shih HP, Seymour PA, Patel NA, Xie R, Wang A, Liu PP et al (2015) A gene regulatory network cooperatively controlled by Pdx1 and Sox9 governs lineage allocation of foregut progenitor cells. Cell Rep 13:326\u2013336","journal-title":"Cell Rep"},{"key":"2109_CR95","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.neuroscience.2016.04.023","volume":"328","author":"V Shinde","year":"2016","unstructured":"Shinde V, Pitale PM, Howse W, Gorbatyuk O, Gorbatyuk M (2016) Neuronatin is a stress-responsive protein of rod photoreceptors. Neuroscience 328:1\u20138","journal-title":"Neuroscience"},{"key":"2109_CR96","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1111\/epi.14618","volume":"60","author":"FM Snoeijen-Schouwenaars","year":"2019","unstructured":"Snoeijen-Schouwenaars FM, van Ool JS, Verhoeven JS, van Mierlo P, Braakman HMH, Smeets EE et al (2019) Diagnostic exome sequencing in 100 consecutive patients with both epilepsy and intellectual disability. Epilepsia 60:155\u2013164","journal-title":"Epilepsia"},{"key":"2109_CR97","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1002\/humu.22844","volume":"36","author":"N Sobreira","year":"2015","unstructured":"Sobreira N, Schiettecatte F, Valle D, Hamosh A (2015) GeneMatcher: a matching tool for connecting investigators with an interest in the same gene. Hum Mutat 36:928\u2013930","journal-title":"Hum Mutat"},{"key":"2109_CR98","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1016\/j.neuroscience.2013.08.050","volume":"253","author":"S Soleman","year":"2013","unstructured":"Soleman S, Filippov MA, Dityatev A, Fawcett JW (2013) Targeting the neural extracellular matrix in neurological disorders. Neuroscience 253:194\u2013213","journal-title":"Neuroscience"},{"key":"2109_CR99","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1038\/ng.3243","volume":"47","author":"P Sulem","year":"2015","unstructured":"Sulem P, Helgason H, Oddson A, Stefansson H, Gudjonsson SA, Zink F et al (2015) Identification of a large set of rare complete human knockouts. Nat Genet 47:448\u2013452","journal-title":"Nat Genet"},{"key":"2109_CR100","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1016\/j.ajhg.2017.02.007","volume":"100","author":"A Ta-Shma","year":"2017","unstructured":"Ta-Shma A, Khan TN, Vivante A, Willer JR, Matak P, Jalas C et al (2017) Mutations in TMEM260 cause a pediatric neurodevelopmental, cardiac, and renal syndrome. Am J Hum Genet 100:666\u2013675","journal-title":"Am J Hum Genet"},{"key":"2109_CR101","doi-asserted-by":"crossref","first-page":"4833","DOI":"10.1021\/pr500229n","volume":"13","author":"GS Tan","year":"2014","unstructured":"Tan GS, Lim KH, Tan HT, Khoo ML, Tan SH, Toh HC et al (2014) Novel proteomic biomarker panel for prediction of aggressive metastatic hepatocellular carcinoma relapse in surgically resectable patients. J Proteome Res 13:4833\u20134846","journal-title":"J Proteome Res"},{"key":"2109_CR102","doi-asserted-by":"crossref","first-page":"15973","DOI":"10.1038\/s41598-018-34238-5","volume":"8","author":"E Tassi","year":"2018","unstructured":"Tassi E, Garman KA, Schmidt MO, Ma X, Kabbara KW, Uren A et al (2018) Fibroblast growth factor binding protein 3 (FGFBP3) impacts carbohydrate and lipid metabolism. Sci Rep 8:15973","journal-title":"Sci Rep"},{"key":"2109_CR103","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1186\/1471-2164-12-505","volume":"12","author":"K Thorsen","year":"2011","unstructured":"Thorsen K, Schepeler T, Oster B, Rasmussen MH, Vang S, Wang K et al (2011) Tumor-specific usage of alternative transcription start sites in colorectal cancer identified by genome-wide exon array analysis. BMC Genom 12:505","journal-title":"BMC Genom"},{"key":"2109_CR104","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1242\/dmm.034546","volume":"11","author":"D Tian","year":"2018","unstructured":"Tian D, Wenlock S, Kabir M, Tzotzos G, Doig AJ, Hentges KE (2018) Identifying mouse developmental essential genes using machine learning. Dis Model Mech 11:4","journal-title":"Dis Model Mech"},{"key":"2109_CR105","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1038\/ejhg.2016.146","volume":"25","author":"D Trujillano","year":"2017","unstructured":"Trujillano D, Bertoli-Avella AM, Kumar Kandaswamy K, Weiss ME, Koster J, Marais A et al (2017) Clinical exome sequencing: results from 2819 samples reflecting 1000 families. Eur J Hum Genet 25:176\u2013182","journal-title":"Eur J Hum Genet"},{"key":"2109_CR106","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1038\/371221a0","volume":"371","author":"FY Tsai","year":"1994","unstructured":"Tsai FY, Keller G, Kuo FC, Weiss M, Chen J, Rosenblatt M et al (1994) An early haematopoietic defect in mice lacking the transcription factor GATA-2. Nature 371:221\u2013226","journal-title":"Nature"},{"key":"2109_CR107","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1684\/epd.2016.0842","volume":"18","author":"J Turnbull","year":"2016","unstructured":"Turnbull J, Tiberia E, Striano P, Genton P, Carpenter S, Ackerley CA et al (2016) Lafora disease. Epilept Disord 18:38\u201362","journal-title":"Epilept Disord"},{"key":"2109_CR108","doi-asserted-by":"crossref","first-page":"7695","DOI":"10.1016\/S0021-9258(19)81292-9","volume":"249","author":"RL Turnquist","year":"1974","unstructured":"Turnquist RL, Gillett TA, Hansen RG (1974) Uridine diphosphate glucose pyrophosphorylase. Crystallization and properties of the enzyme from rabbit liver and species comparisons. J Biol Chem 249:7695\u20137700","journal-title":"J Biol Chem"},{"key":"2109_CR109","first-page":"4","volume":"1","author":"KB Turton","year":"2016","unstructured":"Turton KB, Esnault S, Delain LP, Mosher DF (2016) Merging absolute and relative quantitative PCR data to quantify STAT3 splice variant transcripts. J Vis Exp 1:4","journal-title":"J Vis Exp"},{"key":"2109_CR110","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.matbio.2013.10.002","volume":"35","author":"D Vigetti","year":"2014","unstructured":"Vigetti D, Viola M, Karousou E, De Luca G, Passi A (2014) Metabolic control of hyaluronan synthases. Matrix Biol 35:8\u201313","journal-title":"Matrix Biol"},{"key":"2109_CR111","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/s12957-018-1316-7","volume":"16","author":"L Wang","year":"2018","unstructured":"Wang L, Xiong L, Wu Z, Miao X, Liu Z, Li D et al (2018) Expression of UGP2 and CFL1 expression levels in benign and malignant pancreatic lesions and their clinicopathological significance. World J Surg Oncol 16:11","journal-title":"World J Surg Oncol"},{"key":"2109_CR112","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1080\/07357907.2016.1193745","volume":"34","author":"Q Wang","year":"2016","unstructured":"Wang Q, Yang ZL, Zou Q, Yuan Y, Li J, Liang L et al (2016) SHP2 and UGP2 are biomarkers for progression and poor prognosis of gallbladder cancer. Cancer Invest 34:255\u2013264","journal-title":"Cancer Invest"},{"key":"2109_CR113","doi-asserted-by":"crossref","first-page":"1096","DOI":"10.1126\/science.aac7041","volume":"350","author":"T Wang","year":"2015","unstructured":"Wang T, Birsoy K, Hughes NW, Krupczak KM, Post Y, Wei JJ et al (2015) Identification and characterization of essential genes in the human genome. Science 350:1096\u20131101","journal-title":"Science"},{"key":"2109_CR114","doi-asserted-by":"crossref","first-page":"2592","DOI":"10.1016\/j.bbamcr.2014.06.013","volume":"1843","author":"X Wang","year":"2014","unstructured":"Wang X, Ju L, Fan J, Zhu Y, Liu X, Zhu K et al (2014) Histone H3K4 methyltransferase Mll1 regulates protein glycosylation and tunicamycin-induced apoptosis through transcriptional regulation. Biochim Biophys Acta 1843:2592\u20132602","journal-title":"Biochim Biophys Acta"},{"key":"2109_CR115","doi-asserted-by":"crossref","first-page":"1881","DOI":"10.1038\/s41467-019-09891-7","volume":"10","author":"X Wang","year":"2019","unstructured":"Wang X, Wang S, Troisi EC, Howard TP, Haswell JR, Wolf BK et al (2019) BRD9 defines a SWI\/SNF sub-complex and constitutes a specific vulnerability in malignant rhabdoid tumors. Nat Commun 10:1881","journal-title":"Nat Commun"},{"key":"2109_CR116","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1111\/j.1365-313X.2008.03405.x","volume":"54","author":"MO Woo","year":"2008","unstructured":"Woo MO, Ham TH, Ji HS, Choi MS, Jiang W, Chu SH et al (2008) Inactivation of the UGPase1 gene causes genic male sterility and endosperm chalkiness in rice (Oryza sativa L.). Plant J 54:190\u2013204","journal-title":"Plant J"},{"key":"2109_CR117","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1007\/s11064-012-0938-3","volume":"38","author":"J Xu","year":"2013","unstructured":"Xu J, Song D, Xue Z, Gu L, Hertz L, Peng L (2013) Requirement of glycogenolysis for uptake of increased extracellular K + in astrocytes: potential implications for K + homeostasis and glycogen usage in brain. Neurochem Res 38:472\u2013485","journal-title":"Neurochem Res"},{"key":"2109_CR118","doi-asserted-by":"crossref","first-page":"4386","DOI":"10.1074\/jbc.M115.672931","volume":"291","author":"L Yan","year":"2016","unstructured":"Yan L, Guo H, Hu B, Li R, Yong J, Zhao Y et al (2016) Epigenomic landscape of human fetal brain, heart, and liver. J Biol Chem 291:4386\u20134398","journal-title":"J Biol Chem"},{"key":"2109_CR119","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1038\/s41556-018-0088-1","volume":"20","author":"A Yilmaz","year":"2018","unstructured":"Yilmaz A, Peretz M, Aharony A, Sagi I, Benvenisty N (2018) Defining essential genes for human pluripotent stem cells by CRISPR-Cas9 screening in haploid cells. Nat Cell Biol 20:610\u2013619","journal-title":"Nat Cell Biol"},{"key":"2109_CR120","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1186\/s13059-015-0662-9","volume":"16","author":"D Ying","year":"2015","unstructured":"Ying D, Sham PC, Smith DK, Zhang L, Lau YL, Yang W (2015) HaploShare: identification of extended haplotypes shared by cases and evaluation against controls. Genome Biol 16:92","journal-title":"Genome Biol"},{"key":"2109_CR121","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1042\/BJ20111598","volume":"442","author":"Q Yu","year":"2012","unstructured":"Yu Q, Zheng X (2012) The crystal structure of human UDP-glucose pyrophosphorylase reveals a latch effect that influences enzymatic activity. Biochem J 442:283\u2013291","journal-title":"Biochem J"},{"key":"2109_CR122","doi-asserted-by":"crossref","first-page":"12489","DOI":"10.1002\/jcb.28515","volume":"120","author":"C Zeng","year":"2019","unstructured":"Zeng C, Xing W, Liu Y (2019) Identification of UGP2 as a progression marker that promotes cell growth and motility in human glioma. J Cell Biochem 120:12489\u201312499","journal-title":"J Cell Biochem"},{"key":"2109_CR123","doi-asserted-by":"crossref","first-page":"1523","DOI":"10.1038\/s41467-019-09234-6","volume":"10","author":"Y Zhou","year":"2019","unstructured":"Zhou Y, Zhou B, Pache L, Chang M, Khodabakhshi AH, Tanaseichuk O et al (2019) Metascape provides a biologist-oriented resource for the analysis of systems-level datasets. Nat Commun 10:1523","journal-title":"Nat Commun"}],"container-title":["Acta Neuropathologica"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s00401-019-02109-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s00401-019-02109-6\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s00401-019-02109-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,2,11]],"date-time":"2021-02-11T00:16:49Z","timestamp":1613002609000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/s00401-019-02109-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,12,9]]},"references-count":123,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2020,3]]}},"alternative-id":["2109"],"URL":"https:\/\/doi.org\/10.1007\/s00401-019-02109-6","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/799841","asserted-by":"object"}]},"ISSN":["0001-6322","1432-0533"],"issn-type":[{"value":"0001-6322","type":"print"},{"value":"1432-0533","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,12,9]]},"assertion":[{"value":"25 October 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 December 2019","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 December 2019","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 December 2019","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"value":"KGM, AB, RT and KR are employees of GeneDx, Inc. KR holds stock in OPKO Health, Inc. KKK, PB and ABA are employees of CENTOGENE AG.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}