{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T04:30:51Z","timestamp":1789187451204,"version":"build-2803163510"},"reference-count":32,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2016,1,6]],"date-time":"2016-01-06T00:00:00Z","timestamp":1452038400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0145500","type":"journal-article","created":{"date-parts":[[2016,1,6]],"date-time":"2016-01-06T18:34:50Z","timestamp":1452105290000},"page":"e0145500","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":44,"title":["A Clinical, Neuropathological and Genetic Study of Homozygous A467T POLG-Related Mitochondrial Disease"],"prefix":"10.1371","volume":"11","author":[{"given":"Sanjeev","family":"Rajakulendran","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert D. S.","family":"Pitceathly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan-Willem","family":"Taanman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harry","family":"Costello","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary G.","family":"Sweeney","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cathy E.","family":"Woodward","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zane","family":"Jaunmuktane","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janice L.","family":"Holton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas S.","family":"Jacques","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian N.","family":"Harding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carl","family":"Fratter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael G.","family":"Hanna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shamima","family":"Rahman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2016,1,6]]},"reference":[{"issue":"4","key":"ref1","doi-asserted-by":"crossref","first-page":"a011395","DOI":"10.1101\/cshperspect.a011395","article-title":"Clinical and molecular features of POLG-related mitochondrial disease","volume":"5","author":"JD Stumpf","year":"2013","journal-title":"Cold Spring Harb Perspect Biol"},{"issue":"2","key":"ref2","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1002\/ana.10278","article-title":"Mutations of mitochondrial DNA polymerase gammaA are a frequent cause of autosomal dominant or recessive progressive external ophthalmoplegia","volume":"52","author":"E Lamantea","year":"2002","journal-title":"Ann Neurol"},{"issue":"Pt 7","key":"ref3","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":"R Horvath","year":"2006","journal-title":"Brain"},{"issue":"9437","key":"ref4","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1016\/S0140-6736(04)16983-3","article-title":"Parkinsonism, premature menopause, and mitochondrial DNA polymerase gamma mutations: clinical and molecular genetic study","volume":"364","author":"P Luoma","year":"2004","journal-title":"Lancet"},{"issue":"9","key":"ref5","doi-asserted-by":"crossref","first-page":"1493","DOI":"10.1212\/01.wnl.0000182814.55361.70","article-title":"POLG mutations in Alpers syndrome","volume":"65","author":"KV Nguyen","year":"2005","journal-title":"Neurology"},{"issue":"3","key":"ref6","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1038\/ng759","article-title":"Mutations at the mitochondrial DNA polymerase (POLG) locus associated with male infertility","volume":"29","author":"AT Rovio","year":"2001","journal-title":"Nat Genet"},{"issue":"10","key":"ref7","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":"S Tang","year":"2011","journal-title":"J Med Genet"},{"issue":"Pt 7","key":"ref8","doi-asserted-by":"crossref","first-page":"1685","DOI":"10.1093\/brain\/awl097","article-title":"The spectrum of clinical disease caused by the A467T and W748S POLG mutations: a study of 26 cases","volume":"129","author":"C Tzoulis","year":"2006","journal-title":"Brain"},{"issue":"10","key":"ref9","doi-asserted-by":"crossref","first-page":"2467","DOI":"10.1093\/humrep\/del076","article-title":"Dominant inheritance of premature ovarian failure associated with mutant mitochondrial DNA polymerase gamma","volume":"21","author":"AT Pagnamenta","year":"2006","journal-title":"Hum Reprod"},{"issue":"1","key":"ref10","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1136\/jnnp-2012-303232","article-title":"Distal myopathy with cachexia: an unrecognised phenotype caused by dominantly-inherited mitochondrial polymerase gamma mutations","volume":"84","author":"RD Pitceathly","year":"2013","journal-title":"J Neurol Neurosurg Psychiatry"},{"issue":"14","key":"ref11","doi-asserted-by":"crossref","first-page":"1907","DOI":"10.1093\/hmg\/ddi196","article-title":"Functional defects due to spacer-region mutations of human mitochondrial DNA polymerase in a family with an ataxia-myopathy syndrome","volume":"14","author":"PT Luoma","year":"2005","journal-title":"Hum Mol Genet"},{"issue":"3","key":"ref12","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1038\/90034","article-title":"Mutation of POLG is associated with progressive external ophthalmoplegia characterized by mtDNA deletions","volume":"28","author":"G Van Goethem","year":"2001","journal-title":"Nat Genet"},{"issue":"36","key":"ref13","doi-asserted-by":"crossref","first-page":"31341","DOI":"10.1074\/jbc.M506762200","article-title":"The common A467T mutation in the human mitochondrial DNA polymerase (POLG) compromises catalytic efficiency and interaction with the accessory subunit","volume":"280","author":"SS Chan","year":"2005","journal-title":"J Biol Chem"},{"issue":"8","key":"ref14","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1023\/A:1022881231253","article-title":"Blood mononuclear cell coenzyme Q10 concentration and mitochondrial respiratory chain succinate cytochrome-c reductase activity in phenylketonuric patients","volume":"25","author":"IP Hargreaves","year":"2002","journal-title":"J Inherit Metab Dis"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"e000411","DOI":"10.1136\/bmjopen-2011-000411","article-title":"Hearing in 44\u201345 year olds with m.1555A>G, a genetic mutation predisposing to aminoglycoside-induced deafness: a population based cohort study","volume":"2","author":"S Rahman","year":"2012","journal-title":"BMJ Open"},{"issue":"51","key":"ref16","doi-asserted-by":"crossref","first-page":"36845","DOI":"10.1074\/jbc.M704158200","article-title":"Mitochondrial ND5 gene variation associated with encephalomyopathy and mitochondrial ATP consumption","volume":"282","author":"M McKenzie","year":"2007","journal-title":"J Biol Chem"},{"issue":"7","key":"ref17","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.1111\/epi.12220","article-title":"International consensus classification of hippocampal sclerosis in temporal lobe epilepsy: a Task Force report from the ILAE Commission on Diagnostic Methods","volume":"54","author":"I Blumcke","year":"2013","journal-title":"Epilepsia"},{"issue":"Pt 12","key":"ref18","doi-asserted-by":"crossref","first-page":"3614","DOI":"10.1093\/brain\/aws298","article-title":"What is influencing the phenotype of the common homozygous polymerase-gamma mutation p.Ala467Thr?","volume":"135","author":"VC Neeve","year":"2012","journal-title":"Brain"},{"issue":"2","key":"ref19","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1021\/cr040463d","article-title":"DNA polymerase gamma in mitochondrial DNA replication and repair","volume":"106","author":"MA Graziewicz","year":"2006","journal-title":"Chem Rev"},{"issue":"2","key":"ref20","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":"YS Lee","year":"2009","journal-title":"Cell"},{"issue":"21","key":"ref21","doi-asserted-by":"crossref","first-page":"9072","DOI":"10.1093\/nar\/gkr618","article-title":"Clustering of Alpers disease mutations and catalytic defects in biochemical variants reveal new features of molecular mechanism of the human mitochondrial replicase, Pol gamma","volume":"39","author":"L Euro","year":"2011","journal-title":"Nucleic Acids Res"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1186\/1471-2105-12-402","article-title":"Mitochondrial genome sequence analysis: a custom bioinformatics pipeline substantially improves Affymetrix MitoChip v2.0 call rate and accuracy","volume":"12","author":"HM Xie","year":"2011","journal-title":"BMC Bioinformatics"},{"issue":"4","key":"ref23","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1016\/j.bbrc.2005.05.059","article-title":"A novel mtDNA ND6 gene mutation associated with LHON in a Caucasian family","volume":"332","author":"SI Zhadanov","year":"2005","journal-title":"Biochem Biophys Res Commun"},{"issue":"5","key":"ref24","doi-asserted-by":"crossref","first-page":"1152","DOI":"10.1086\/339933","article-title":"Reduced-median-network analysis of complete mitochondrial DNA coding-region sequences for the major African, Asian, and European haplogroups","volume":"70","author":"C Herrnstadt","year":"2002","journal-title":"Am J Hum Genet"},{"issue":"12","key":"ref25","doi-asserted-by":"crossref","first-page":"1811","DOI":"10.1212\/01.WNL.0000098997.23471.65","article-title":"Patient homozygous for a recessive POLG mutation presents with features of MERRF","volume":"61","author":"G Van Goethem","year":"2003","journal-title":"Neurology"},{"issue":"2","key":"ref26","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1002\/mus.21494","article-title":"Sensory ataxic neuropathy dysarthria and ophthalmoparesis (SANDO) in a sibling pair with a homozygous p.A467T POLG mutation","volume":"41","author":"JC McHugh","year":"2010","journal-title":"Muscle Nerve"},{"issue":"2","key":"ref27","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1007\/s10545-008-1038-z","article-title":"Clinical and molecular features of mitochondrial DNA depletion syndromes","volume":"32","author":"A Spinazzola","year":"2009","journal-title":"J Inherit Metab Dis"},{"issue":"11","key":"ref28","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1136\/jmg.2009.067686","article-title":"The unfolding clinical spectrum of POLG mutations","volume":"46","author":"MJ Blok","year":"2009","journal-title":"J Med Genet"},{"issue":"5","key":"ref29","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1007\/s00415-011-6268-6","article-title":"Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE)-like phenotype: an expanded clinical spectrum of POLG1 mutations","volume":"259","author":"S Tang","year":"2012","journal-title":"J Neurol"},{"issue":"Pt 3","key":"ref30","doi-asserted-by":"crossref","first-page":"818","DOI":"10.1093\/brain\/awn007","article-title":"POLG1 mutations cause a syndromic epilepsy with occipital lobe predilection","volume":"131","author":"BA Engelsen","year":"2008","journal-title":"Brain"},{"issue":"11","key":"ref31","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1212\/WNL.0b013e3181b78488","article-title":"Ataxia with ophthalmoplegia or sensory neuropathy is frequently caused by POLG mutations","volume":"73","author":"C Schulte","year":"2009","journal-title":"Neurology"},{"issue":"7","key":"ref32","doi-asserted-by":"crossref","first-page":"1204","DOI":"10.1212\/01.WNL.0000156516.77696.5A","article-title":"Autosomal recessive mitochondrial ataxic syndrome due to mitochondrial polymerase gamma mutations","volume":"64","author":"S Winterthun","year":"2005","journal-title":"Neurology"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0145500","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,9,13]],"date-time":"2020-09-13T17:11:28Z","timestamp":1600017088000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0145500"}},"subtitle":[],"editor":[{"given":"Sherine Swee Lin","family":"Chan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2016,1,6]]},"references-count":32,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2016,1,6]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0145500","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,1,6]]}}}