{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T23:23:20Z","timestamp":1778801000956,"version":"3.51.4"},"reference-count":37,"publisher":"Elsevier BV","issue":"4","license":[{"start":{"date-parts":[[2021,4,1]],"date-time":"2021-04-01T00:00:00Z","timestamp":1617235200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2021,4,1]],"date-time":"2021-04-01T00:00:00Z","timestamp":1617235200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2021,1,11]],"date-time":"2021-01-11T00:00:00Z","timestamp":1610323200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005760","name":"G\u00f6teborgs Universitet","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005760","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","nmd-journal.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Neuromuscular Disorders"],"published-print":{"date-parts":[[2021,4]]},"DOI":"10.1016\/j.nmd.2021.01.004","type":"journal-article","created":{"date-parts":[[2021,1,13]],"date-time":"2021-01-13T19:42:46Z","timestamp":1610566966000},"page":"348-358","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":4,"title":["Functional analysis of a novel POL\u03b3A mutation associated with a severe perinatal mitochondrial encephalomyopathy"],"prefix":"10.1016","volume":"31","author":[{"given":"Niklas","family":"Darin","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Triinu","family":"Siibak","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bradley","family":"Peter","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carola","family":"Hedberg-Oldfors","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gittan","family":"Kollberg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vassili","family":"Kalbin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ali-Reza","family":"Moslemi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bertil","family":"Macao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anders","family":"Oldfors","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Falkenberg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1016\/j.nmd.2021.01.004_bib0001","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1016\/j.cell.2009.07.050","article-title":"Structural insight into processive human mitochondrial DNA synthesis and disease-related polymerase mutations","volume":"139","author":"Lee","year":"2009","journal-title":"Cell"},{"key":"10.1016\/j.nmd.2021.01.004_bib0002","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1007\/BF01799602","article-title":"Structure and function of the mitochondrial genome","volume":"15","author":"Clayton","year":"1992","journal-title":"J Inherit Metab Dis"},{"key":"10.1016\/j.nmd.2021.01.004_bib0003","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.gde.2016.03.005","article-title":"Human mitochondrial DNA replication machinery and disease","volume":"38","author":"Young","year":"2016","journal-title":"Curr Opin Genet Dev"},{"key":"10.1016\/j.nmd.2021.01.004_bib0004","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/j.nmd.2007.11.005","article-title":"155th ENMC workshop: polymerase gamma and disorders of mitochondrial DNA synthesis, 21-23 September 2007, Naarden, The Netherlands","volume":"18","author":"Chinnery","year":"2008","journal-title":"Neuromuscul Disord"},{"key":"10.1016\/j.nmd.2021.01.004_bib0005","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1146\/annurev.biochem.76.060305.152028","article-title":"DNA replication and transcription in mammalian mitochondria","volume":"76","author":"Falkenberg","year":"2007","journal-title":"Annu Rev Biochem"},{"key":"10.1016\/j.nmd.2021.01.004_bib0006","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1093\/brain\/awh410","article-title":"Infantile hepatocerebral syndromes associated with mutations in the mitochondrial DNA polymerase-gammaA","volume":"128","author":"Ferrari","year":"2005","journal-title":"Brain"},{"key":"10.1016\/j.nmd.2021.01.004_bib0007","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1002\/ana.20498","article-title":"POLG mutations and Alpers syndrome","volume":"57","author":"Davidzon","year":"2005","journal-title":"Ann Neurol"},{"key":"10.1016\/j.nmd.2021.01.004_bib0008","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1002\/ana.20079","article-title":"POLG mutations associated with Alpers' syndrome and mitochondrial DNA depletion","volume":"55","author":"Naviaux","year":"2004","journal-title":"Ann Neurol"},{"key":"10.1016\/j.nmd.2021.01.004_bib0009","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1016\/j.ejpn.2011.12.006","article-title":"Phenotypic and genotypic variability in Alpers syndrome","volume":"16","author":"Sofou","year":"2012","journal-title":"Eur J Paediatr Neurol"},{"key":"10.1016\/j.nmd.2021.01.004_bib0010","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1212\/01.wnl.0000345002.47396.e1","article-title":"Fatal congenital myopathy and gastrointestinal pseudo-obstruction due to POLG1 mutations","volume":"72","author":"Giordano","year":"2009","journal-title":"Neurology"},{"key":"10.1016\/j.nmd.2021.01.004_bib0011","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1016\/S0022-3476(05)80734-6","article-title":"Mitochondrial encephalomyopathies in childhood. I. Biochemical and morphologic investigations [see comments]","volume":"119","author":"Tulinius","year":"1991","journal-title":"J Pediatr"},{"key":"10.1016\/j.nmd.2021.01.004_bib0012","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1212\/WNL.53.1.79","article-title":"Autosomal dominant progressive external ophthalmoplegia: distribution of multiple mitochondrial DNA deletions","volume":"53","author":"Moslemi","year":"1999","journal-title":"Neurology"},{"key":"10.1016\/j.nmd.2021.01.004_bib0013","doi-asserted-by":"crossref","first-page":"2411","DOI":"10.1093\/hmg\/ddt094","article-title":"Subnormal levels of POLgammaA cause inefficient initiation of light-strand DNA synthesis and lead to mitochondrial DNA deletions and progressive external ophthalmoplegia [corrected]","volume":"22","author":"Roos","year":"2013","journal-title":"Hum Mol Genet"},{"key":"10.1016\/j.nmd.2021.01.004_bib0014","doi-asserted-by":"crossref","first-page":"D1251","DOI":"10.1093\/nar\/gkv1003","article-title":"MitoCarta2.0: an updated inventory of mammalian mitochondrial proteins","volume":"44","author":"Calvo","year":"2016","journal-title":"Nucl Acids Res"},{"key":"10.1016\/j.nmd.2021.01.004_bib0015","doi-asserted-by":"crossref","first-page":"2423","DOI":"10.1038\/sj.emboj.7600257","article-title":"Reconstitution of a minimal mtDNA replisome in vitro","volume":"23","author":"Korhonen","year":"2004","journal-title":"EMBO J"},{"key":"10.1016\/j.nmd.2021.01.004_bib0016","doi-asserted-by":"crossref","first-page":"e391","DOI":"10.1212\/NXG.0000000000000391","article-title":"Deep sequencing of mitochondrial DNA and characterization of a novel POLG mutation in a patient with arPEO","volume":"6","author":"Hedberg-Oldfors","year":"2020","journal-title":"Neurol Genet"},{"key":"10.1016\/j.nmd.2021.01.004_bib0017","doi-asserted-by":"crossref","first-page":"5258","DOI":"10.1021\/bi048135v","article-title":"Thermodynamic stability of carbonic anhydrase: measurements of binding affinity and stoichiometry using ThermoFluor","volume":"44","author":"Matulis","year":"2005","journal-title":"Biochemistry"},{"key":"10.1016\/j.nmd.2021.01.004_bib0018","doi-asserted-by":"crossref","first-page":"8808","DOI":"10.1038\/ncomms9808","article-title":"Complementation between polymerase- and exonuclease-deficient mitochondrial DNA polymerase mutants in genomically engineered flies","volume":"6","author":"Bratic","year":"2015","journal-title":"Nat Commun"},{"key":"10.1016\/j.nmd.2021.01.004_bib0019","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/j.nmd.2015.01.004","article-title":"The in cis T251I and P587L POLG1 base changes: description of a new family and literature review","volume":"25","author":"Scuderi","year":"2015","journal-title":"Neuromuscul Disord"},{"key":"10.1016\/j.nmd.2021.01.004_bib0020","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1093\/protein\/10.1.7","article-title":"Prediction of the stability of protein mutants based on structural environment-dependent amino acid substitution and propensity tables","volume":"10","author":"Topham","year":"1997","journal-title":"Protein Eng"},{"key":"10.1016\/j.nmd.2021.01.004_bib0021","doi-asserted-by":"crossref","first-page":"18586","DOI":"10.1073\/pnas.0609020103","article-title":"Mitochondrial deoxynucleotide pool sizes in mouse liver and evidence for a transport mechanism for thymidine monophosphate","volume":"103","author":"Ferraro","year":"2006","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1016\/j.nmd.2021.01.004_bib0022","doi-asserted-by":"crossref","first-page":"e66","DOI":"10.1093\/nar\/gky203","article-title":"Simultaneous determination of ribonucleoside and deoxyribonucleoside triphosphates in biological samples by hydrophilic interaction liquid chromatography coupled with tandem mass spectrometry","volume":"46","author":"Kong","year":"2018","journal-title":"Nucl Acids Res"},{"key":"10.1016\/j.nmd.2021.01.004_bib0023","doi-asserted-by":"crossref","first-page":"16992","DOI":"10.1074\/jbc.M111.236968","article-title":"Nucleoside triphosphate pool asymmetry in mammalian mitochondria","volume":"286","author":"Wheeler","year":"2011","journal-title":"J Biol Chem"},{"key":"10.1016\/j.nmd.2021.01.004_bib0024","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.ejpn.2012.09.005","article-title":"Cerebrospinal fluid biomarkers in neurological diseases in children","volume":"17","author":"Shahim","year":"2013","journal-title":"Eur J Paediatr Neurol"},{"key":"10.1016\/j.nmd.2021.01.004_bib0025","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.1038\/gim.2017.35","article-title":"The clinical spectrum and natural history of early-onset diseases due to DNA polymerase gamma mutations","volume":"19","author":"Hikmat","year":"2017","journal-title":"Genet Med"},{"key":"10.1016\/j.nmd.2021.01.004_bib0026","doi-asserted-by":"crossref","first-page":"1674","DOI":"10.1093\/brain\/awl088","article-title":"Phenotypic spectrum associated with mutations of the mitochondrial polymerase gamma gene","volume":"129","author":"Horvath","year":"2006","journal-title":"Brain"},{"key":"10.1016\/j.nmd.2021.01.004_bib0027","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1212\/WNL.0b013e31820e7b25","article-title":"POLG1 manifestations in childhood","volume":"76","author":"Isohanni","year":"2011","journal-title":"Neurology"},{"key":"10.1016\/j.nmd.2021.01.004_bib0028","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1002\/humu.20852","article-title":"Analysis of mutant DNA polymerase gamma in patients with mitochondrial DNA depletion","volume":"30","author":"Taanman","year":"2009","journal-title":"Hum Mutat"},{"key":"10.1016\/j.nmd.2021.01.004_bib0029","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1016\/j.bbabio.2014.01.021","article-title":"Mapping 136 pathogenic mutations into functional modules in human DNA polymerase gamma establishes predictive genotype-phenotype correlations for the complete spectrum of POLG syndromes","volume":"1837","author":"Farnum","year":"2014","journal-title":"Biochim Biophys Acta"},{"key":"10.1016\/j.nmd.2021.01.004_bib0030","doi-asserted-by":"crossref","first-page":"1959","DOI":"10.15252\/embj.201591520","article-title":"Structural basis for processivity and antiviral drug toxicity in human mitochondrial DNA replicase","volume":"34","author":"Szymanski","year":"2015","journal-title":"EMBO J"},{"key":"10.1016\/j.nmd.2021.01.004_bib0031","doi-asserted-by":"crossref","first-page":"4198","DOI":"10.1074\/jbc.M116.773341","article-title":"Synergistic effects of the in cis T251I and P587L mitochondrial dna polymerase gamma disease mutations","volume":"292","author":"DeBalsi","year":"2017","journal-title":"J Biol Chem"},{"key":"10.1016\/j.nmd.2021.01.004_bib0032","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1136\/jmedgenet-2011-100222","article-title":"Mitochondrial DNA polymerase gamma mutations: an ever expanding molecular and clinical spectrum","volume":"48","author":"Tang","year":"2011","journal-title":"J Med Genet"},{"key":"10.1016\/j.nmd.2021.01.004_bib0033","doi-asserted-by":"crossref","first-page":"902","DOI":"10.1093\/nar\/gkl1116","article-title":"The accessory subunit B of DNA polymerase gamma is required for mitochondrial replisome function","volume":"35","author":"Farge","year":"2007","journal-title":"Nucl Acids Res"},{"key":"10.1016\/j.nmd.2021.01.004_bib0034","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1038\/sj.ejhg.5201341","article-title":"Low frequency of mtDNA point mutations in patients with PEO associated with POLG1 mutations","volume":"13","author":"Kollberg","year":"2005","journal-title":"Eur J Hum Genet"},{"key":"10.1016\/j.nmd.2021.01.004_bib0035","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1002\/mus.21636","article-title":"Sensory ataxic neuropathy with dysarthria and ophthalmoparesis (SANDO) in late life due to compound heterozygous POLG mutations","volume":"41","author":"Weiss","year":"2010","journal-title":"Muscle Nerve"},{"key":"10.1016\/j.nmd.2021.01.004_bib0036","doi-asserted-by":"crossref","DOI":"10.1136\/bcr-2013-010343","article-title":"Diagnostic challenges in movement disorders: sensory Ataxia Neuropathy Dysarthria and Ophthalmoplegia (SANDO) syndrome","volume":"2013","author":"Lovan","year":"2013","journal-title":"BMJ Case Rep"},{"key":"10.1016\/j.nmd.2021.01.004_bib0037","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1002\/ana.24922","article-title":"Deoxycytidine and deoxythymidine treatment for thymidine kinase 2 deficiency","volume":"81","author":"Lopez-Gomez","year":"2017","journal-title":"Ann Neurol"}],"container-title":["Neuromuscular Disorders"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0960896621000055?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0960896621000055?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,18]],"date-time":"2025-10-18T08:10:23Z","timestamp":1760775023000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0960896621000055"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4]]},"references-count":37,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2021,4]]}},"alternative-id":["S0960896621000055"],"URL":"https:\/\/doi.org\/10.1016\/j.nmd.2021.01.004","relation":{},"ISSN":["0960-8966"],"issn-type":[{"value":"0960-8966","type":"print"}],"subject":[],"published":{"date-parts":[[2021,4]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Functional analysis of a novel POL\u03b3A mutation associated with a severe perinatal mitochondrial encephalomyopathy","name":"articletitle","label":"Article Title"},{"value":"Neuromuscular Disorders","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.nmd.2021.01.004","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2021 The Author(s). Published by Elsevier B.V.","name":"copyright","label":"Copyright"}]}}