{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T01:00:59Z","timestamp":1790816459558,"version":"4.1.0"},"reference-count":34,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"8","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2017,8,2]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              Precision medicine is an emerging approach to disease treatment and prevention that takes into account individual variability in the environment, lifestyle, and genetic makeup of patients. Patient\u2010specific human induced pluripotent stem cells hold promise to transform precision medicine into real\u2010life clinical practice. Lamin A\/C (\n              <jats:styled-content style=\"fixed-case\">LMNA<\/jats:styled-content>\n              )\u2010related cardiomyopathy is the most common inherited cardiomyopathy in which a substantial proportion of mutations in the\n              <jats:italic>\n                <jats:styled-content style=\"fixed-case\">LMNA<\/jats:styled-content>\n              <\/jats:italic>\n              gene are of nonsense mutation.\n              <jats:styled-content style=\"fixed-case\">PTC<\/jats:styled-content>\n              124 induces translational read\u2010through over the premature stop codon and restores production of the full\u2010length proteins from the affected genes. In this study we generated human induced pluripotent stem cells\u2010derived cardiomyocytes from patients who harbored different\n              <jats:italic>\n                <jats:styled-content style=\"fixed-case\">LMNA<\/jats:styled-content>\n              <\/jats:italic>\n              mutations (nonsense and frameshift) to evaluate the potential therapeutic effects of\n              <jats:styled-content style=\"fixed-case\">PTC<\/jats:styled-content>\n              124 in\n              <jats:italic>\n                <jats:styled-content style=\"fixed-case\">LMNA<\/jats:styled-content>\n              <\/jats:italic>\n              \u2010related cardiomyopathy.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              We generated human induced pluripotent stem cells lines from 3 patients who carried distinctive mutations (R225X, Q354X, and T518fs) in the\n              <jats:italic>\n                <jats:styled-content style=\"fixed-case\">LMNA<\/jats:styled-content>\n              <\/jats:italic>\n              gene. The cardiomyocytes derived from these human induced pluripotent stem cells lines reproduced the pathophysiological hallmarks of\n              <jats:italic>\n                <jats:styled-content style=\"fixed-case\">LMNA<\/jats:styled-content>\n              <\/jats:italic>\n              \u2010related cardiomyopathy. Interestingly,\n              <jats:styled-content style=\"fixed-case\">PTC<\/jats:styled-content>\n              124 treatment increased the production of full\u2010length LMNA proteins in only the R225X mutant, not in other mutations. Functional evaluation experiments on the R225X mutant further demonstrated that\n              <jats:styled-content style=\"fixed-case\">PTC<\/jats:styled-content>\n              124 treatment not only reduced nuclear blebbing and electrical stress\u2010induced apoptosis but also improved the excitation\u2010contraction coupling of the affected cardiomyocytes.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              Using cardiomyocytes derived from human induced pluripotent stem cells carrying different\n              <jats:italic>\n                <jats:styled-content style=\"fixed-case\">LMNA<\/jats:styled-content>\n              <\/jats:italic>\n              mutations, we demonstrated that the effect of\n              <jats:styled-content style=\"fixed-case\">PTC<\/jats:styled-content>\n              124 is codon selective. A premature stop codon\n              <jats:styled-content style=\"fixed-case\">UGA<\/jats:styled-content>\n              appeared to be most responsive to\n              <jats:styled-content style=\"fixed-case\">PTC<\/jats:styled-content>\n              124 treatment.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.117.005677","type":"journal-article","created":{"date-parts":[[2017,7,29]],"date-time":"2017-07-29T00:10:26Z","timestamp":1501287026000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":64,"title":["Modeling Treatment Response for Lamin A\/C Related Dilated Cardiomyopathy in Human Induced Pluripotent Stem Cells"],"prefix":"10.1161","volume":"6","author":[{"given":"Yee\u2010Ki","family":"Lee","sequence":"first","affiliation":[{"name":"Cardiology Division, Department of Medicine, Li Ka Shing Faculty of Medicine The University of Hong Kong, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yee\u2010Man","family":"Lau","sequence":"additional","affiliation":[{"name":"Cardiology Division, Department of Medicine, Li Ka Shing Faculty of Medicine The University of Hong Kong, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhu\u2010Jun","family":"Cai","sequence":"additional","affiliation":[{"name":"Cardiology Division, Department of Medicine, Li Ka Shing Faculty of Medicine The University of Hong Kong, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wing\u2010Hon","family":"Lai","sequence":"additional","affiliation":[{"name":"Cardiology Division, Department of Medicine, Li Ka Shing Faculty of Medicine The University of Hong Kong, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lai\u2010Yung","family":"Wong","sequence":"additional","affiliation":[{"name":"Cardiology Division, Department of Medicine, Li Ka Shing Faculty of Medicine The University of Hong Kong, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hung\u2010Fat","family":"Tse","sequence":"additional","affiliation":[{"name":"Cardiology Division, Department of Medicine, Li Ka Shing Faculty of Medicine The University of Hong Kong, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kwong\u2010Man","family":"Ng","sequence":"additional","affiliation":[{"name":"Cardiology Division, Department of Medicine, Li Ka Shing Faculty of Medicine The University of Hong Kong, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chung\u2010Wah","family":"Siu","sequence":"additional","affiliation":[{"name":"Cardiology Division, Department of Medicine, Li Ka Shing Faculty of Medicine The University of Hong Kong, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)85424-8"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrg1906"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.genom.7.080505.115732"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.18632\/aging.100383"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.2006.00677.x"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI37679"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.hfc.2009.11.003"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1097\/HCO.0b013e328337ba52"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2007.11.008"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature05756"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0711795105"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1177\/0091270006297140"},{"key":"e_1_3_4_14_2","unstructured":"Clinicaltrials.gov . A phase 3 efficacy and safety study of ataluren (PTC124\u00ae) in patients with nonsense mutation cystic fibrosis. https:\/\/clinicaltrials.gov\/ct2\/show\/study\/NCT02139306. Accessed January 1 2017."},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/dds556"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.115.019847"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2015.11.101"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.18632\/aging.100277"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.18632\/aging.100503"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-013-1414-x"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2016.01.083"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1089\/cell.2010.0051"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2012.150"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1113\/expphysiol.2006.033894"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1002\/dmrr.2304"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12265-013-9510-z"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0019787"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1620\/tjem.218.309"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ahj.2007.07.038"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200419448"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.18632\/aging.100414"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(01)00583-9"},{"key":"e_1_3_4_33_2","unstructured":"National Institutes of Health . Precision medicine initiative cohort program. https:\/\/www-nih-gov.eproxy1.lib.hku.hk\/precision-medicine-initiative-cohort-program. Accessed January 13 2016."},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMp1500523"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCEP.116.004227"}],"container-title":["Journal of the American Heart Association"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/JAHA.117.005677","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T10:54:30Z","timestamp":1715597670000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/JAHA.117.005677"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,8,2]]},"references-count":34,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2017,8,2]]}},"alternative-id":["10.1161\/JAHA.117.005677"],"URL":"https:\/\/doi.org\/10.1161\/jaha.117.005677","relation":{},"ISSN":["2047-9980"],"issn-type":[{"value":"2047-9980","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,8,2]]},"assertion":[{"value":"2017-01-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-05-02","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-07-28","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e005677"}}