{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T05:35:50Z","timestamp":1761197750904,"version":"build-2065373602"},"reference-count":38,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2020,1,26]],"date-time":"2020-01-26T00:00:00Z","timestamp":1579996800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Mitochondrial dysfunction is known to play a key role in the pathophysiological pathway of neurodegenerative disorders. Nuclear-encoded proteins are involved in mtDNA replication, including DNA polymerase gamma, which is the only known replicative mtDNA polymerase, encoded by nuclear genes Polymerase gamma 1 (POLG) and Polymerase gamma 2 (POLG2). POLG mutations are well-known as a frequent cause of mitochondrial myopathies of nuclear origin. However, only rare descriptions of POLG2 mutations leading to mitochondriopathies exist. Here we describe a 68-year-old woman presenting with a 20-year history of camptocormia, mild proximal weakness, and moderate CK increase. Muscle histology showed COX-negative fibres. Genetic analysis by next generation sequencing revealed an already reported heterozygous c.1192-8_1207dup24 mutation in the POLG2 gene. This is the first report on a POLG2 mutation leading to camptocormia as the main clinical phenotype, extending the phenotypic spectrum of POLG2 associated diseases. This underlines the broad phenotypic spectrum found in mitochondrial diseases, especially in mitochondrial disorders of nuclear origin.<\/jats:p>","DOI":"10.3390\/diagnostics10020068","type":"journal-article","created":{"date-parts":[[2020,1,27]],"date-time":"2020-01-27T07:41:11Z","timestamp":1580110871000},"page":"68","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Camptocormia as a Novel Phenotype in a Heterozygous POLG2 Mutation"],"prefix":"10.3390","volume":"10","author":[{"given":"Diana","family":"Lehmann Urban","sequence":"first","affiliation":[{"name":"Department of Neurology, Ulm University, 89081 Ulm, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leila","family":"Motlagh Scholle","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Halle\/S., 06120 Halle, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kerstin","family":"Alt","sequence":"additional","affiliation":[{"name":"Genetikum, 89231 Neu-Ulm, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Albert C.","family":"Ludolph","sequence":"additional","affiliation":[{"name":"Department of Neurology, Ulm University, 89081 Ulm, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angela","family":"Rosenbohm","sequence":"additional","affiliation":[{"name":"Department of Neurology, Ulm University, 89081 Ulm, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,1,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.nmd.2014.09.008","article-title":"A novel m.7539C>T point mutation in the mt-tRNA(Asp) gene associated with multisystemic mitochondrial disease","volume":"25","author":"Lehmann","year":"2015","journal-title":"Neuromuscul. Disord."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1007\/s13311-013-0177-6","article-title":"Mitochondrial DNA depletion syndromes: Review and updates of genetic basis, manifestations, and therapeutic options","volume":"10","author":"Scaglia","year":"2013","journal-title":"Neurotherapeutics"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1007\/s10072-016-2734-3","article-title":"Novel POLG mutations and variable clinical phenotypes in 13 Italian patients","volume":"38","author":"Cardaioli","year":"2017","journal-title":"Neurol. Sci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1216","DOI":"10.1177\/0883073814537380","article-title":"Defects of mitochondrial DNA replication","volume":"29","author":"Copeland","year":"2014","journal-title":"J. Child. Neurol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1016\/j.ejmg.2016.08.012","article-title":"Whole exome sequencing identifies a homozygous POLG2 missense variant in an infant with fulminant hepatic failure and mitochondrial DNA depletion","volume":"59","author":"Varma","year":"2016","journal-title":"Eur. J. Med. Genet."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1136\/jmg.2008.058180","article-title":"Novel POLG1 mutations associated with neuromuscular and liver phenotypes in adults and children","volume":"46","author":"Stewart","year":"2009","journal-title":"J. Med. Genet."},{"key":"ref_7","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":"Dermaut","year":"2001","journal-title":"Nat. Genet."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1517","DOI":"10.1007\/s00415-010-5565-9","article-title":"Late-onset ptosis and myopathy in a patient with a heterozygous insertion in POLG2","volume":"257","author":"Walter","year":"2010","journal-title":"J. Neurol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1026","DOI":"10.1086\/504303","article-title":"Mutant POLG2 disrupts DNA polymerase gamma subunits and causes progressive external ophthalmoplegia","volume":"78","author":"Longley","year":"2006","journal-title":"Am. J. Hum. Gene"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1002\/acn3.361","article-title":"POLG2 deficiency causes adult-onset syndromic sensory neuropathy, ataxia and parkinsonism","volume":"4","author":"Besse","year":"2017","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3052","DOI":"10.1093\/hmg\/ddr209","article-title":"Biochemical analysis of human POLG2 variants associated with mitochondrial disease","volume":"20","author":"Young","year":"2011","journal-title":"Hum. Mol. Genet."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1212\/CPJ.0000000000000453","article-title":"Camptocormia: Etiology, diagnosis, and treatment response","volume":"8","author":"Ali","year":"2018","journal-title":"Neurol. Clin. Pract."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1007\/s00401-011-0818-y","article-title":"A new phenotype of mitochondrial disease characterized by familial late-onset predominant axial myopathy and encephalopathy","volume":"121","author":"Sakiyama","year":"2011","journal-title":"Acta Neuropathol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/S0248-8663(01)00530-6","article-title":"Camptocormia: A sign of axial myopathy. Report of 7 cases","volume":"23","author":"Delcey","year":"2002","journal-title":"Rev. Med. Interne."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1007\/s10067-006-0259-5","article-title":"Camptocormia as a clinical manifestation of mitochondrial myopathy","volume":"26","author":"Peris","year":"2007","journal-title":"Clin. Rheumatol."},{"key":"ref_16","first-page":"159","article-title":"Camptocormia in the elderly patient: Myopathy or muscular dystonia?","volume":"60","author":"Poullin","year":"1993","journal-title":"Rev. Rhum. Ed. Fr."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1002\/mds.10385","article-title":"Severe forward flexion of the trunk in Parkinson\u2019s disease: Focal myopathy of the paraspinal muscles mimicking camptocormia","volume":"18","author":"Schabitz","year":"2003","journal-title":"Mov. Disord."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1136\/jnnp.60.1.51","article-title":"Bent spine syndrome","volume":"60","author":"Serratrice","year":"1996","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e147","DOI":"10.1212\/NXG.0000000000000147","article-title":"Camptocormia and shuffling gait due to a novel MT-TV mutation: Diagnostic pitfalls","volume":"3","author":"Reimann","year":"2017","journal-title":"Neurol. Genet."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/S0005-2728(02)00305-5","article-title":"Mitochondrial respiratory rates and activities of respiratory chain complexes correlate linearly with heteroplasmy of deleted mtDNA without threshold and independently of deletion size","volume":"1556","author":"Gellerich","year":"2002","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_21","unstructured":"(2020, January 25). megSAP\u2014A Medical Genetics Sequence Analysis Pipeline. Available online: https:\/\/github.com\/imgag\/megSAP."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Sturm, M., Schroeder, C., and Bauer, P. (2016). SeqPurge: Highly-sensitive adapter trimming for paired-end NGS data. BMC Bioinform., 17.","DOI":"10.1186\/s12859-016-1069-7"},{"key":"ref_23","unstructured":"Li, H. (2013). Aligning sequence reads, clone sequences and assemblycontigs with BWA-MEM. arXiv."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2813","DOI":"10.1093\/bioinformatics\/btu376","article-title":"ABRA: Improved coding indel detection via assembly-based realignment","volume":"30","author":"Mose","year":"2014","journal-title":"Bioinformatics"},{"key":"ref_25","unstructured":"Garrison, E., and Marth, G. (2012). Haplotype-based variant detection from short-read sequencing. arXiv."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"80","DOI":"10.4161\/fly.19695","article-title":"A program for annotating and predicting the effects of single nucleotide polymorphisms, SnpEff: SNPs in the genome of Drosophila melanogaster strain w1118; iso-2; iso-3","volume":"6","author":"Cingolani","year":"2012","journal-title":"Fly (Austin)"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1038\/nature19057","article-title":"Analysis of protein-coding genetic variation in 60,706 humans","volume":"536","author":"Lek","year":"2016","journal-title":"Nature"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1038\/nature15393","article-title":"A global reference for human genetic variation","volume":"526","author":"Auton","year":"2015","journal-title":"Nature"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"D1062","DOI":"10.1093\/nar\/gkx1153","article-title":"ClinVar: Improving access to variant interpretations and supporting evidence","volume":"46","author":"Landrum","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"ref_30","unstructured":"(2020, January 25). ngs-bits\u2014Short-read sequencing tools for diagnostics: GSvar. Available online: https:\/\/github.com\/imgag\/ngs-bits."},{"key":"ref_31","first-page":"564","article-title":"HGVS Recommendations for the Description of SequenceVariants: 2016 Update","volume":"6","author":"Dalgleish","year":"2016","journal-title":"Hum. Mutat."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1159\/000117217","article-title":"Ragged red or ragged blue fibers","volume":"36","author":"Reichmann","year":"1996","journal-title":"Eur. Neurol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.jns.2016.06.062","article-title":"The wide POLG-related spectrum: An. integrated view","volume":"368","author":"Bereau","year":"2016","journal-title":"J. Neurol Sci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1111\/neup.12173","article-title":"Frequencies of myohistological mitochondrial changes in patients with mitochondrial DNA deletions and the common m.3243A>G point mutation","volume":"35","author":"Zierz","year":"2015","journal-title":"Neuropathology"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1086","DOI":"10.1111\/ene.12989","article-title":"Is deltoid muscle biopsy useful in isolated camptocormia? A prospective study","volume":"23","author":"Chanson","year":"2016","journal-title":"Eur. J. Neurol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/s13395-015-0035-9","article-title":"Oxidative stress, mitochondrial damage, and cores in muscle from calsequestrin-1 knockout mice","volume":"5","author":"Paolini","year":"2015","journal-title":"Skelet. Muscle"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1186\/1750-1172-2-25","article-title":"Central core disease","volume":"2","author":"Jungbluth","year":"2007","journal-title":"Orphanet. J. Rare Dis."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"930","DOI":"10.1016\/S0960-8966(02)00135-9","article-title":"The spectrum of pathology in central core disease","volume":"12","author":"Sewry","year":"2002","journal-title":"Neuromuscul. Disord."}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/10\/2\/68\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T14:08:35Z","timestamp":1760364515000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/10\/2\/68"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,1,26]]},"references-count":38,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2020,2]]}},"alternative-id":["diagnostics10020068"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics10020068","relation":{},"ISSN":["2075-4418"],"issn-type":[{"type":"electronic","value":"2075-4418"}],"subject":[],"published":{"date-parts":[[2020,1,26]]}}}