{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T13:01:22Z","timestamp":1793278882108,"version":"4.5.0"},"reference-count":41,"publisher":"Elsevier BV","issue":"4","license":[{"start":{"date-parts":[[2018,4,1]],"date-time":"2018-04-01T00:00:00Z","timestamp":1522540800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2018,4,1]],"date-time":"2018-04-01T00:00:00Z","timestamp":1522540800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2018,10,5]],"date-time":"2018-10-05T00:00:00Z","timestamp":1538697600000},"content-version":"vor","delay-in-days":187,"URL":"http:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"}],"funder":[{"DOI":"10.13039\/501100021356","name":"Fondation du Grand d\u00e9fi Pierre Lavoie","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100021356","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008582","name":"McGill University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008582","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008644","name":"Faculty of Medicine, McGill University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008644","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100013020","name":"Compute Canada","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100013020","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["201610PJT- 377869"],"award-info":[{"award-number":["201610PJT- 377869"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["MOP-G2-341146-159133-BRIDG"],"award-info":[{"award-number":["MOP-G2-341146-159133-BRIDG"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000156","name":"Fonds de Recherche du Qu\u00e9bec - Sant\u00e9","doi-asserted-by":"publisher","award":["201512MSH-360766-171036"],"award-info":[{"award-number":["201512MSH-360766-171036"]}],"id":[{"id":"10.13039\/501100000156","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["cell.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["The American Journal of Human Genetics"],"published-print":{"date-parts":[[2018,4]]},"DOI":"10.1016\/j.ajhg.2018.02.011","type":"journal-article","created":{"date-parts":[[2018,3,22]],"date-time":"2018-03-22T11:44:44Z","timestamp":1521719084000},"page":"676-684","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":87,"title":["Bi-allelic Mutations in EPRS, Encoding the Glutamyl-Prolyl-Aminoacyl-tRNA Synthetase, Cause a Hypomyelinating Leukodystrophy"],"prefix":"10.1016","volume":"102","author":[{"given":"Marisa I.","family":"Mendes","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariana","family":"Gutierrez Salazar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kether","family":"Guerrero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle","family":"Thiffault","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gajja S.","family":"Salomons","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurence","family":"Gauquelin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luan T.","family":"Tran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diane","family":"Forget","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-Soleil","family":"Gauthier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quinten","family":"Waisfisz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Desiree E.C.","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cas","family":"Simons","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marjo S.","family":"van der Knaap","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iris","family":"Marquardt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aida","family":"Lemes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanna","family":"Mierzewska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernhard","family":"Weschke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang","family":"Koehler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benoit","family":"Coulombe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole I.","family":"Wolf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Genevi\u00e8ve","family":"Bernard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ajhg.2018.02.011_bib1","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1097\/00019052-200404000-00017","article-title":"The latest on leukodystrophies","volume":"17","author":"Schiffmann","year":"2004","journal-title":"Curr. Opin. Neurol."},{"key":"10.1016\/j.ajhg.2018.02.011_bib2","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1212\/01.wnl.0000343049.00540.c8","article-title":"Invited article: an MRI-based approach to the diagnosis of white matter disorders","volume":"72","author":"Schiffmann","year":"2009","journal-title":"Neurology"},{"key":"10.1016\/j.ajhg.2018.02.011_bib3","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1055\/s-0036-1588020","article-title":"Update on Leukodystrophies: A Historical Perspective and Adapted Definition","volume":"47","author":"Kevelam","year":"2016","journal-title":"Neuropediatrics"},{"key":"10.1016\/j.ajhg.2018.02.011_bib4","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1016\/j.ymgme.2014.12.434","article-title":"A clinical approach to the diagnosis of patients with leukodystrophies and genetic leukoencephelopathies","volume":"114","author":"Parikh","year":"2015","journal-title":"Mol. Genet. Metab."},{"key":"10.1016\/j.ajhg.2018.02.011_bib5","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1002\/ana.24650","article-title":"Whole exome sequencing in patients with white matter abnormalities","volume":"79","author":"Vanderver","year":"2016","journal-title":"Ann. Neurol."},{"key":"10.1016\/j.ajhg.2018.02.011_bib6","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1002\/ana.24167","article-title":"Mutations in RARS cause hypomyelination","volume":"76","author":"Wolf","year":"2014","journal-title":"Ann. Neurol."},{"key":"10.1016\/j.ajhg.2018.02.011_bib7","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1016\/j.ajhg.2013.04.006","article-title":"Mutations in DARS cause hypomyelination with brain stem and spinal cord involvement and leg spasticity","volume":"92","author":"Taft","year":"2013","journal-title":"Am. J. Hum. Genet."},{"key":"10.1016\/j.ajhg.2018.02.011_bib8","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1006\/jmbi.2000.4242","article-title":"Macromolecular assemblage of aminoacyl-tRNA synthetases: quantitative analysis of protein-protein interactions and mechanism of complex assembly","volume":"304","author":"Robinson","year":"2000","journal-title":"J.\u00a0Mol. Biol."},{"key":"10.1016\/j.ajhg.2018.02.011_bib9","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1146\/annurev.bi.56.070187.001013","article-title":"Aminoacyl tRNA synthetases: general scheme of structure-function relationships in the polypeptides and recognition of transfer RNAs","volume":"56","author":"Schimmel","year":"1987","journal-title":"Annu. Rev. Biochem."},{"key":"10.1016\/j.ajhg.2018.02.011_bib10","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1016\/j.molcel.2007.11.038","article-title":"An important role for the multienzyme aminoacyl-tRNA synthetase complex in mammalian translation and cell growth","volume":"29","author":"Kyriacou","year":"2008","journal-title":"Mol. Cell"},{"key":"10.1016\/j.ajhg.2018.02.011_bib11","doi-asserted-by":"crossref","first-page":"4872","DOI":"10.1128\/MCB.00711-13","article-title":"A multiple aminoacyl-tRNA synthetase complex that enhances tRNA-aminoacylation in African trypanosomes","volume":"33","author":"Cestari","year":"2013","journal-title":"Mol. Cell. Biol."},{"key":"10.1016\/j.ajhg.2018.02.011_bib12","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.cell.2004.09.030","article-title":"Noncanonical function of glutamyl-prolyl-tRNA synthetase: gene-specific silencing of translation","volume":"119","author":"Sampath","year":"2004","journal-title":"Cell"},{"key":"10.1016\/j.ajhg.2018.02.011_bib13","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1016\/j.molcel.2008.01.010","article-title":"WHEP domains direct noncanonical function of glutamyl-Prolyl tRNA synthetase in translational control of gene expression","volume":"29","author":"Jia","year":"2008","journal-title":"Mol. Cell"},{"key":"10.1016\/j.ajhg.2018.02.011_bib14","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.cell.2012.02.018","article-title":"Coding region polyadenylation generates a truncated tRNA synthetase that counters translation repression","volume":"149","author":"Yao","year":"2012","journal-title":"Cell"},{"key":"10.1016\/j.ajhg.2018.02.011_bib15","doi-asserted-by":"crossref","first-page":"2971","DOI":"10.1093\/brain\/awq257","article-title":"Magnetic resonance imaging pattern recognition in hypomyelinating disorders","volume":"133","author":"Steenweg","year":"2010","journal-title":"Brain"},{"key":"10.1016\/j.ajhg.2018.02.011_bib16","doi-asserted-by":"crossref","first-page":"7623","DOI":"10.1038\/ncomms8623","article-title":"Recessive mutations in POLR1C cause a leukodystrophy by impairing biogenesis of RNA polymerase III","volume":"6","author":"Thiffault","year":"2015","journal-title":"Nat. Commun."},{"key":"10.1016\/j.ajhg.2018.02.011_bib17","doi-asserted-by":"crossref","first-page":"15615","DOI":"10.1038\/ncomms15615","article-title":"R2TP\/Prefoldin-like component RUVBL1\/RUVBL2 directly interacts with ZNHIT2 to regulate assembly of U5 small nuclear ribonucleoprotein","volume":"8","author":"Cloutier","year":"2017","journal-title":"Nat. Commun."},{"key":"10.1016\/j.ajhg.2018.02.011_bib18","doi-asserted-by":"crossref","first-page":"e1003210","DOI":"10.1371\/journal.pgen.1003210","article-title":"A newly uncovered group of distantly related lysine methyltransferases preferentially interact with molecular chaperones to regulate their activity","volume":"9","author":"Cloutier","year":"2013","journal-title":"PLoS Genet."},{"key":"10.1016\/j.ajhg.2018.02.011_bib19","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1042\/bj2980395","article-title":"Characterization and kinetic analysis of the intracellular domain of human protein tyrosine phosphatase beta (HPTP beta) using synthetic phosphopeptides","volume":"298","author":"Harder","year":"1994","journal-title":"Biochem. J."},{"key":"10.1016\/j.ajhg.2018.02.011_bib20","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1038\/nmeth.2557","article-title":"The CRAPome: a contaminant repository for affinity purification-mass spectrometry data","volume":"10","author":"Mellacheruvu","year":"2013","journal-title":"Nat. Methods"},{"key":"10.1016\/j.ajhg.2018.02.011_bib21","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1016\/j.ymeth.2007.02.018","article-title":"Affinity-purification mass spectrometry (AP-MS) of serine\/threonine phosphatases","volume":"42","author":"Chen","year":"2007","journal-title":"Methods"},{"key":"10.1016\/j.ajhg.2018.02.011_bib22","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1021\/pr300778b","article-title":"Discovery of cell compartment specific protein-protein\u00a0interactions using affinity purification combined with tandem mass spectrometry","volume":"12","author":"Lavall\u00e9e-Adam","year":"2013","journal-title":"J.\u00a0Proteome Res."},{"key":"10.1016\/j.ajhg.2018.02.011_bib23","doi-asserted-by":"crossref","first-page":"3551","DOI":"10.1002\/(SICI)1522-2683(19991201)20:18<3551::AID-ELPS3551>3.0.CO;2-2","article-title":"Probability-based protein identification by searching sequence databases using mass spectrometry data","volume":"20","author":"Perkins","year":"1999","journal-title":"Electrophoresis"},{"key":"10.1016\/j.ajhg.2018.02.011_bib24","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1038\/ng2013","article-title":"Mitochondrial aspartyl-tRNA synthetase deficiency causes leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation","volume":"39","author":"Scheper","year":"2007","journal-title":"Nat. Genet."},{"key":"10.1016\/j.ajhg.2018.02.011_bib25","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1016\/j.ajhg.2010.10.016","article-title":"Pelizaeus-Merzbacher-like disease caused by AIMP1\/p43 homozygous mutation","volume":"87","author":"Feinstein","year":"2010","journal-title":"Am. J. Hum. Genet."},{"key":"10.1016\/j.ajhg.2018.02.011_bib26","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1016\/j.ajhg.2015.02.012","article-title":"Loss-of-function alanyl-tRNA synthetase mutations cause an autosomal-recessive early-onset epileptic encephalopathy with persistent myelination defect","volume":"96","author":"Simons","year":"2015","journal-title":"Am. J. Hum. Genet."},{"key":"10.1016\/j.ajhg.2018.02.011_bib27","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.1086\/375039","article-title":"Glycyl tRNA synthetase mutations in Charcot-Marie-Tooth disease type 2D and distal spinal muscular atrophy type V","volume":"72","author":"Antonellis","year":"2003","journal-title":"Am. J. Hum. Genet."},{"key":"10.1016\/j.ajhg.2018.02.011_bib28","doi-asserted-by":"crossref","first-page":"2161","DOI":"10.1093\/brain\/awv158","article-title":"Loss of function mutations in HARS cause a spectrum of inherited peripheral neuropathies","volume":"138","author":"Safka Brozkova","year":"2015","journal-title":"Brain"},{"key":"10.1016\/j.ajhg.2018.02.011_bib29","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1016\/j.ajhg.2010.09.008","article-title":"Compound heterozygosity for loss-of-function lysyl-tRNA synthetase mutations in a patient with peripheral neuropathy","volume":"87","author":"McLaughlin","year":"2010","journal-title":"Am. J. Hum. Genet."},{"key":"10.1016\/j.ajhg.2018.02.011_bib30","doi-asserted-by":"crossref","first-page":"1247","DOI":"10.1136\/jnnp-2013-305049","article-title":"Exome sequencing identifies a significant variant in methionyl-tRNA synthetase (MARS) in a family with late-onset CMT2","volume":"84","author":"Gonzalez","year":"2013","journal-title":"J.\u00a0Neurol. Neurosurg. Psychiatry"},{"key":"10.1016\/j.ajhg.2018.02.011_bib31","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1016\/j.ajhg.2014.03.003","article-title":"Mutations in QARS, encoding glutaminyl-tRNA synthetase, cause progressive microcephaly, cerebral-cerebellar atrophy, and intractable seizures","volume":"94","author":"Zhang","year":"2014","journal-title":"Am. J. Hum. Genet."},{"key":"10.1016\/j.ajhg.2018.02.011_bib32","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1111\/cge.12327","article-title":"Rare variants in methionyl- and tyrosyl-tRNA synthetase genes in late-onset autosomal dominant Charcot-Marie-Tooth neuropathy","volume":"86","author":"Hyun","year":"2014","journal-title":"Clin. Genet."},{"key":"10.1016\/j.ajhg.2018.02.011_bib33","doi-asserted-by":"crossref","first-page":"2063","DOI":"10.1212\/WNL.0000000000000497","article-title":"Novel (ovario) leukodystrophy related to AARS2 mutations","volume":"82","author":"Dallabona","year":"2014","journal-title":"Neurology"},{"key":"10.1016\/j.ajhg.2018.02.011_bib34","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1111\/j.1399-0004.2011.01644.x","article-title":"A novel homozygous mutation of DARS2 may cause a severe LBSL variant","volume":"80","author":"Miyake","year":"2011","journal-title":"Clin. Genet."},{"key":"10.1016\/j.ajhg.2018.02.011_bib35","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.1093\/brain\/aws070","article-title":"Leukoencephalopathy with thalamus and brainstem involvement and high lactate \u2018LTBL\u2019 caused by EARS2 mutations","volume":"135","author":"Steenweg","year":"2012","journal-title":"Brain"},{"key":"10.1016\/j.ajhg.2018.02.011_bib36","doi-asserted-by":"crossref","first-page":"4521","DOI":"10.1093\/hmg\/dds294","article-title":"Mitochondrial phenylalanyl-tRNA synthetase mutations underlie fatal infantile Alpers encephalopathy","volume":"21","author":"Elo","year":"2012","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.ajhg.2018.02.011_bib37","doi-asserted-by":"crossref","first-page":"6543","DOI":"10.1073\/pnas.1103471108","article-title":"Mutations in mitochondrial histidyl tRNA synthetase HARS2 cause ovarian dysgenesis and sensorineural hearing loss of Perrault syndrome","volume":"108","author":"Pierce","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.ajhg.2018.02.011_bib38","doi-asserted-by":"crossref","first-page":"e1001288","DOI":"10.1371\/journal.pbio.1001288","article-title":"Mutations in the mitochondrial methionyl-tRNA synthetase cause a neurodegenerative phenotype in flies and a recessive ataxia (ARSAL) in humans","volume":"10","author":"Bayat","year":"2012","journal-title":"PLoS Biol."},{"key":"10.1016\/j.ajhg.2018.02.011_bib39","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1086\/521227","article-title":"Deleterious mutation in the mitochondrial arginyl-transfer RNA synthetase gene is associated with pontocerebellar hypoplasia","volume":"81","author":"Edvardson","year":"2007","journal-title":"Am. J. Hum. Genet."},{"key":"10.1016\/j.ajhg.2018.02.011_bib40","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1002\/humu.22590","article-title":"VARS2 and TARS2 mutations in patients with mitochondrial encephalomyopathies","volume":"35","author":"Diodato","year":"2014","journal-title":"Hum. Mutat."},{"key":"10.1016\/j.ajhg.2018.02.011_bib41","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1038\/s10038-017-0363-1","article-title":"Homozygosity for a nonsense variant in AIMP2 is associated with a progressive neurodevelopmental disorder with microcephaly, seizures, and spastic quadriparesis","volume":"63","author":"Shukla","year":"2018","journal-title":"J. Hum. Genet."}],"container-title":["The American Journal of Human Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0002929718300569?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0002929718300569?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T10:17:35Z","timestamp":1762078655000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0002929718300569"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,4]]},"references-count":41,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2018,4]]}},"alternative-id":["S0002929718300569"],"URL":"https:\/\/doi.org\/10.1016\/j.ajhg.2018.02.011","relation":{},"ISSN":["0002-9297"],"issn-type":[{"value":"0002-9297","type":"print"}],"subject":[],"published":{"date-parts":[[2018,4]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Bi-allelic Mutations in EPRS, Encoding the Glutamyl-Prolyl-Aminoacyl-tRNA Synthetase, Cause a Hypomyelinating Leukodystrophy","name":"articletitle","label":"Article Title"},{"value":"The American Journal of Human Genetics","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ajhg.2018.02.011","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2018 American Society of Human Genetics.","name":"copyright","label":"Copyright"}]}}