{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T21:41:52Z","timestamp":1790977312992,"version":"4.1.0"},"reference-count":146,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2010,7,21]],"date-time":"2010-07-21T00:00:00Z","timestamp":1279670400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["WIREs RNA"],"published-print":{"date-parts":[[2010,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Mitochondrial (mt\u2010) tRNA (\n                    <jats:italic>MTT<\/jats:italic>\n                    ) gene mutations are an important cause of human morbidity and are associated with a wide range of pathology, from isolated organ\u2010specific diseases such as myopathy or hearing loss, through to multisystem disorders with encephalopathy, gastrointestinal dysmotility, and life\u2010threatening cardiomyopathy. Our understanding of how\n                    <jats:italic>MTT<\/jats:italic>\n                    mutations cause disease remains poor and progress has been hampered by the complex interaction of genotype with phenotype that can result in patients who harbor the same mutation exhibiting starkly contrasting phenotypes, whereas other (genetically heterogeneous) patients manifest clinically identical syndromes. A further complexity is the highly polymorphic nature of mitochondrial DNA (mtDNA), which must temper any reflex assumptions of pathogenicity for novel\n                    <jats:italic>MTT<\/jats:italic>\n                    substitutions. Nevertheless significant progress is being made and we shall review the methods employed to identify and characterize\n                    <jats:italic>MTT<\/jats:italic>\n                    mutations as pathogenic. Also important is our understanding of the molecular processes involved and we shall discuss the data available on two of the most studied\n                    <jats:italic>MTT<\/jats:italic>\n                    mutations (m.8344A &gt; G and m.3243A &gt; G) as well as other potential pathogenic mechanisms. Knowledge of factors influencing the inheritance of\n                    <jats:italic>MTT<\/jats:italic>\n                    mutations, and therefore the likelihood of disease transmission, is of particular importance to female patients. At present, the factors determining transmission remain elusive, but we shall examine several possible mechanisms and discuss the evidence for each. Finally, a number of different yeast and mouse models are currently used to investigate mitochondrial disease and we will assess the importance of and difficulties associated with each model as well as the future of possible therapies for patients with mitochondrial disease. Copyright \u00a9 2010 John Wiley &amp; Sons, Inc.\n                  <\/jats:p>\n                  <jats:p>\n                    This article is categorized under:\n                    <jats:list list-type=\"explicit-label\">\n                      <jats:list-item>\n                        <jats:p>RNA in Disease and Development &gt; RNA in Disease<\/jats:p>\n                      <\/jats:list-item>\n                    <\/jats:list>\n                  <\/jats:p>","DOI":"10.1002\/wrna.27","type":"journal-article","created":{"date-parts":[[2010,7,21]],"date-time":"2010-07-21T08:17:30Z","timestamp":1279700250000},"page":"304-324","source":"Crossref","is-referenced-by-count":162,"title":["Mitochondrial tRNA mutations and disease"],"prefix":"10.1002","volume":"1","author":[{"given":"John W.","family":"Yarham","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna L.","family":"Elson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma L.","family":"Blakely","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"McFarland","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert W.","family":"Taylor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2010,7,21]]},"reference":[{"key":"e_1_2_12_1_2_1","unstructured":"The MitoMAP database an online compendium of human mitochondrial DNA variation can be accessed athttp:\/\/www.mitomap.org\/MITOMAPThe Mamit\u2010tRNA database (http:\/\/mamit\u2010trna.u\u2010strasbg.fr\/) provides information on mammalian tRNA sequences and 2\u2010D structures as well as details of human mt\u2010tRNA mutations linked with 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