{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T04:19:53Z","timestamp":1768882793904,"version":"3.49.0"},"reference-count":18,"publisher":"Wiley","issue":"S3","license":[{"start":{"date-parts":[[2010,5,11]],"date-time":"2010-05-11T00:00:00Z","timestamp":1273536000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[2010,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Mitochondrial tRNA<jats:sup>Leu(UUR)<\/jats:sup> mutation m.3302A\u2009&gt;\u2009G is associated with respiratory chain complex I deficiency and has been described as a rare cause of mostly adult\u2010onset slowly progressive myopathy. Five families with 11 patients have been described so far; 5 of them died young due to cardiorespiratory failure. Here, we report on a segregation study in a family with an index patient who already presented at the age of 18 months with proximal muscular hypotonia, abnormal fatigability, and lactic acidosis. This early\u2010onset myopathy was rapidly progressive. At 8 years, the patient is wheel\u2010chair bound, requires nocturnal assisted ventilation, and suffers from recurrent respiratory infections. Severe complex I deficiency and nearly homoplasmy for m.3302A\u2009&gt;\u2009G were found in muscle. We collected blood, hair, buccal swabs and muscle biopsies from asymptomatic adults in this pedigree and determined heteroplasmy levels in these tissues as well as OXPHOS activities in muscle. All participating asymptomatic adults had normal OXPHOS activities. In contrast to earlier reports, we found surprisingly little variation of heteroplasmy levels in different tissues of the same individual. Up to 45% mutation load in muscle and up to 38% mutation load in other tissues were found in non\u2010affected adults. The phenotypic spectrum of tRNA<jats:sup>Leu(UUR)<\/jats:sup> m.3302A\u2009&gt;\u2009G mutation seems to be wider than previously described. A threshold of more than 45% heteroplasmy in muscle seems to be necessary to alter complex I activity leading to clinical manifestation. The presented data may be helpful for prognostic considerations and counseling in affected families.<\/jats:p>","DOI":"10.1007\/s10545-010-9098-2","type":"journal-article","created":{"date-parts":[[2010,5,10]],"date-time":"2010-05-10T08:08:47Z","timestamp":1273478927000},"page":"219-226","source":"Crossref","is-referenced-by-count":9,"title":["Mitochondrial tRNA<sup>Leu(UUR)<\/sup> mutation m.3302A\u2009&gt;\u2009G presenting as childhood\u2010onset severe myopathy: threshold determination through segregation study"],"prefix":"10.1002","volume":"33","author":[{"given":"Diana","family":"Ballhausen","sequence":"first","affiliation":[{"name":"Division of Molecular Pediatrics Centre Hospitalier Universitaire Vaudois CI 02\u201335, Av. P. Decker 2 Lausanne 1011 Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fr\u00e9d\u00e9ric","family":"Guerry","sequence":"additional","affiliation":[{"name":"Medical Genetics Centre Hospitalier Universitaire Vaudois Lausanne Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dagmar","family":"Hahn","sequence":"additional","affiliation":[{"name":"University Institute of Clinical Chemistry Inselspital Bern Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andr\u00e9","family":"Schaller","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Division of Human Genetics Inselspital Bern Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean\u2010Marc","family":"Nuoffer","sequence":"additional","affiliation":[{"name":"University Institute of Clinical Chemistry Inselspital Bern Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luisa","family":"Bonaf\u00e9","sequence":"additional","affiliation":[{"name":"Division of Molecular Pediatrics Centre Hospitalier Universitaire Vaudois CI 02\u201335, Av. P. Decker 2 Lausanne 1011 Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pierre\u2010Yves","family":"Jeannet","sequence":"additional","affiliation":[{"name":"Neuropediatrics Centre Hospitalier Universitaire Vaudois Lausanne Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sebastien","family":"Jacquemont","sequence":"additional","affiliation":[{"name":"Medical Genetics Centre Hospitalier Universitaire Vaudois Lausanne Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2010,5,11]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/13779"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)36552-4"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0091-679X(01)65006-4"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.62.12.1920"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2004.02.008"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkl727"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-8966(00)00101-2"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.b94"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-4889(03)00105-8"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/0009-8981(94)90055-8"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1515\/BC.2001.144"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj1140597"},{"key":"e_1_2_6_14_1","first-page":"949","article-title":"A novel tRNA leu(UUR) mutation in childhood mitochondrial myopathy","volume":"53","author":"Shoffner JM","year":"1993","journal-title":"Am J Hum Genet"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/0009-8981(84)90149-9"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2004.06.004"},{"key":"e_1_2_6_17_1","unstructured":"WallaceDC LottMT(2009)MITOMAP: a human mitochondrial genome database.http:\/\/www.mitomap.org."},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI114409"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1097\/WCO.0b013e3282ef58cd"}],"container-title":["Journal of Inherited Metabolic Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1007\/s10545-010-9098-2","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,15]],"date-time":"2023-09-15T06:20:50Z","timestamp":1694758850000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1007\/s10545-010-9098-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,5,11]]},"references-count":18,"journal-issue":{"issue":"S3","published-print":{"date-parts":[[2010,12]]}},"alternative-id":["10.1007\/s10545-010-9098-2"],"URL":"https:\/\/doi.org\/10.1007\/s10545-010-9098-2","archive":["Portico"],"relation":{},"ISSN":["0141-8955","1573-2665"],"issn-type":[{"value":"0141-8955","type":"print"},{"value":"1573-2665","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,5,11]]}}}