{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T18:26:31Z","timestamp":1770747991012,"version":"3.49.0"},"reference-count":24,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2018,12,4]],"date-time":"2018-12-04T00:00:00Z","timestamp":1543881600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"ZonMW Priority Medicines","award":["113302003"],"award-info":[{"award-number":["113302003"]}]},{"name":"Stichting Energy4All"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp; Gen Med"],"published-print":{"date-parts":[[2019,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The mitochondrial DNA m.3243A&gt;G mutation is one the most prevalent mutation causing mitochondrial disease in adult patients. Several cohort studies have used heteroplasmy levels in urinary epithelial cells (UEC) to correlate the genotype of the patients to the clinical severity. However, the interpretation of these data is hampered by a lack of knowledge on the intra\u2010patient variability of the heteroplasmy levels. The goal of this study was to determine the day\u2010to\u2010day variation of the heteroplasmy levels in UEC.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Fifteen carriers of the m.3243A&gt;G mutation collected five urine samples in a 14\u2010day window. Heteroplasmy levels of the m.3243A&gt;G mutation were determined in these samples. Data from the national cohort study, including Newcastle Mitochondrial Disease Adult Scale scores and clinical diagnosis, were used.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In the samples of six patients, heteroplasmy levels were within a 5% margin. In the samples collected from five patients, the margin was &gt;20%.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Heteroplasmy levels of UEC in carriers of the m.3243A&gt;G mutation have a significant day\u2010to\u2010day variation. The interpretation of a correlation between heteroplasmy levels in urine and disease severity is therefore not reliable. Therefore, heteroplasmy levels in UEC should not be used as a prognostic biomarker in these patients.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.523","type":"journal-article","created":{"date-parts":[[2018,12,5]],"date-time":"2018-12-05T05:09:54Z","timestamp":1543986594000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Intra\u2010patient variability of heteroplasmy levels in urinary epithelial cells in carriers of the m.3243A&gt;G mutation"],"prefix":"10.1002","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2541-3090","authenticated-orcid":false,"given":"Paul","family":"de Laat","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Radboudumc Amalia Childrens Hospital Radboud Center for Mitochondrial Medicine Nijmegen The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard J.","family":"Rodenburg","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Radboudumc Amalia Childrens Hospital Radboud Center for Mitochondrial Medicine Nijmegen The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan A. M.","family":"Smeitink","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Radboudumc Amalia Childrens Hospital Radboud Center for Mitochondrial Medicine Nijmegen The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mirian C. H.","family":"Janssen","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Radboudumc Amalia Childrens Hospital Radboud Center for Mitochondrial Medicine Nijmegen The Netherlands"},{"name":"Department of Internal Medicine, Radboudumc Radboud Center for Mitochondrial Medicine Nijmegen The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,12,4]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/120.10.1713"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/1531-8249(200008)48:2<188::AID-ANA8>3.0.CO;2-P"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2009.03.002"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-012-9465-2"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2013.05.013"},{"issue":"1","key":"e_1_2_9_7_1","first-page":"30","article-title":"Dysphagia, malnutrition and gastrointestinal problems in patients with mitochondrial disease caused by the m3243A%3eG mutation","volume":"73","author":"Laat P.","year":"2015","journal-title":"Netherlands Journal of Medicine"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2016.06.003"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2005.039339"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/348651a0"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.201708262"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-291X(05)80860-5"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00246-003-0490-7"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jfma.2011.06.014"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfh546"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mito.2009.01.004"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1086\/301959"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mito.2006.12.004"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jocn.2008.11.012"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2012-303528"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410160409"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1086\/316930"},{"issue":"2","key":"e_1_2_9_23_1","first-page":"147","article-title":"Renal epithelial fragments in urine sediment","volume":"25","author":"Schumann G. B. G.","year":"1981","journal-title":"Acta Cytologica"},{"issue":"5","key":"e_1_2_9_24_1","first-page":"368","article-title":"Mutation in mitochondrial tRNA(Leu)(UUR) gene in a large pedigree with maternally transmitted type II diabetes mellitus and deafness","volume":"1","author":"Ouweland J. M.","year":"1992","journal-title":"NatureGenetics"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000342121.91336.4d"}],"container-title":["Molecular Genetics &amp; Genomic Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fmgg3.523","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mgg3.523","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,14]],"date-time":"2023-09-14T19:47:58Z","timestamp":1694720878000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mgg3.523"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,12,4]]},"references-count":24,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2019,2]]}},"alternative-id":["10.1002\/mgg3.523"],"URL":"https:\/\/doi.org\/10.1002\/mgg3.523","archive":["Portico"],"relation":{},"ISSN":["2324-9269","2324-9269"],"issn-type":[{"value":"2324-9269","type":"print"},{"value":"2324-9269","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,12,4]]},"assertion":[{"value":"2018-07-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-10-17","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-12-04","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e00523"}}