{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T07:26:48Z","timestamp":1786606008455,"version":"build-2736575974"},"reference-count":72,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:00:00Z","timestamp":1786492800000},"content-version":"vor","delay-in-days":223,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100004731","name":"Natural Science Foundation of Zhejiang Province","doi-asserted-by":"publisher","award":["LHZY24H020002"],"award-info":[{"award-number":["LHZY24H020002"]}],"id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004731","name":"Natural Science Foundation of Zhejiang Province","doi-asserted-by":"publisher","award":["LZ22H190002"],"award-info":[{"award-number":["LZ22H190002"]}],"id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Human Mutation"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:p>\n                    Mutations in mitochondrial tRNA (mt\u2010tRNA) are found to be associated with hypertrophic cardiomyopathy (HCM), but their molecular mechanisms remain largely undetermined. In this study, we investigated the contribution of a novel HCM\u2010related mt\u2010tRNA\n                    <jats:sup>Ser(AGY)<\/jats:sup>\n                    12234A\u2009&gt;\u2009G mutation to the phenotypic expression of the mt\u2010tRNA\n                    <jats:sup>Ile<\/jats:sup>\n                    4263A\u2009&gt;\u2009G mutation in two genetically unrelated Han Chinese pedigrees. Strikingly, the penetrance and expressivity of one pedigree (HCM2) with both m.4263A\u2009&gt;\u2009G and m.12234A\u2009&gt;\u2009G mutations are much higher than another pedigree (HCM1) with only m.4263A\u2009&gt;\u2009G mutation. By molecular level, the homoplasmic m.4263A\u2009&gt;\u2009G mutation is located at the processing site for the tRNA\n                    <jats:sup>Ile<\/jats:sup>\n                    5\u2009\n                    <jats:sup>\u2032<\/jats:sup>\n                    \u2010end precursor, disrupting a conserved Watson\u2013Crick base pairing (1A\u201369T) which is believed to cause mitochondrial dysfunction. Moreover, the heteroplasmic m.12234A\u2009&gt;\u2009G mutation occurs at an extremely conserved nucleotide in the anticodon stem of tRNA\n                    <jats:sup>Ser(AGY)<\/jats:sup>\n                    , a position which is critical for tRNA structure and function. Using trans\u2010mitochondrial cell models, we demonstrated that cybrids with both mt\u2010tRNA mutations exhibited more severe mitochondrial dysfunctions than cybrids with only the m.4263A\u2009&gt;\u2009G mutation. Furthermore, a marked decrease in mt\u2010RNA transcripts was observed in cells harboring both m.4263A\u2009&gt;\u2009G and m.12234A\u2009&gt;\u2009G mutations. Taken together, our study indicated that the m.12234A\u2009&gt;\u2009G mutation acted in synergy with the m.4263A\u2009&gt;\u2009G mutation, triggering mitochondrial dysfunctions and contributing to a high penetrance of HCM in a pedigree harboring both mtDNA mutations.\n                  <\/jats:p>","DOI":"10.1155\/humu\/6788682","type":"journal-article","created":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T06:27:41Z","timestamp":1786602461000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mitochondrial tRNA\n                    <sup>Ser(AGY)<\/sup>\n                    12234A\u2009&gt;\u2009G Mutation May Contribute to the Clinical Expression of Hypertrophic Cardiomyopathy\u2010Associated tRNA\n                    <sup>Ile<\/sup>\n                    4263A\u2009&gt;\u2009G 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