{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T18:40:23Z","timestamp":1792521623475,"version":"4.5.0"},"reference-count":47,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Genomic and Precision Medicine"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>\n                      Duchenne muscular dystrophy (DMD) is a severe X-linked neuromuscular disease caused by mutations in the\n                      <jats:italic toggle=\"yes\">DMD<\/jats:italic>\n                      gene, leading to the absence or dysfunction of dystrophin. Although cardiac and skeletal muscles are both affected, tissue-specific differences in disease manifestation and dystrophin regulation remain poorly understood.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>To investigate these differences, we established a human induced pluripotent stem cell model of DMD from peripheral blood mononuclear cells of a patient (DMD patient with a point mutation in intron 68 (c.9975-1G&gt;T) investigated in the study [DMB15]) carrying a splice-site mutation in intron 68 (c.9975-1G&gt;T). An isogenic control line was generated via clustered regularly interspaced short palindromic repeats\/clustered regularly interspaced short palindromic repeats\u2013associated protein 9 (CRIPSR\/Cas9) correction. Both repaired and DMD human induced pluripotent stem cells were differentiated into cardiomyocytes (DMB15-CMs) and skeletal muscle cells (DMB15-derived skeletal muscle cells); the skeletal muscle lineage included a myoblast (DMB15-derived myoblasts) stage. Transcript and protein analyses were performed, along with functional assessments using microelectrode array recordings and calcium handling analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>\n                      Transcript analysis revealed an in-frame deletion of 2 amino acids (Tyr3325 and Arg3326) due to skipping of the first 6 nucleotides of exon 69. Despite this, near full-length Dp427 (full-length dystrophin isoform of 427 kDa) was detected by Western blot, along with expression of Dp116 (dystrophin isoform of 116 kDa) in DMB15-CMs. Dystrophin levels were preserved in DMD DMB15-CMs but markedly reduced in DMB15-derived skeletal muscle cells, suggesting tissue-specific regulation. Analysis of DMB15-derived myoblasts demonstrated possible changes in myogenic program activation, alongside inconsistent expression of utrophin, the dystrophin paralogue. Functional analysis showed altered \u03b2-adrenergic responsiveness in DMD DMB15-CMs, with increased beating frequency and accelerated repolarization on isoproterenol stimulation. DMB15-CMs showed largely preserved basal Ca\n                      <jats:sup>2+<\/jats:sup>\n                      cycling but failed to maintain a normal amplitude response under \u03b2-adrenergic stimulation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>\n                      Our study identifies a splice-site\n                      <jats:italic toggle=\"yes\">DMD<\/jats:italic>\n                      gene mutation that preserves high levels of dystrophin expression in cardiac muscle but reduced in skeletal muscle and reveals Dp116 expression in cardiomyocytes. These findings highlight the importance of tissue context in DMD and demonstrate the power of human induced pluripotent stem cell\u2013based systems for dissecting mutation-specific effects.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circgen.125.005376","type":"journal-article","created":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T09:00:16Z","timestamp":1790326816000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Gene-Corrected Human iPSC\u2013Derived Cardiomyocytes and Skeletal Muscles Reveal Partial Dystrophin Dp427 Preservation and Cardiac Dp116 Expression in Duchenne Muscular Dystrophy Patient With a Splice-Site Mutation in Intron 68 (c.9975-1G&gt;T)"],"prefix":"10.1161","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-0770-1109","authenticated-orcid":true,"given":"Marta","family":"Bia\u0142obrzeska","sequence":"first","affiliation":[{"name":"Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology (M.B., M.P., I.V., J.S., U.F.-S., J.D.), Jagiellonian University, Krakow, Poland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2555-7839","authenticated-orcid":true,"given":"Marta","family":"Przymusza\u0142a","sequence":"additional","affiliation":[{"name":"Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology (M.B., M.P., I.V., J.S., U.F.-S., J.D.), Jagiellonian University, Krakow, Poland."},{"name":"Doctoral School of Exact and Natural Sciences (M.P.), Jagiellonian University, Krakow, Poland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5582-6588","authenticated-orcid":true,"given":"Pawel E","family":"Ferdek","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Faculty of Biochemistry, Biophysics and Biotechnology (P.F.), Jagiellonian University, Krakow, Poland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iryna","family":"Viestia","sequence":"additional","affiliation":[{"name":"Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology (M.B., M.P., I.V., J.S., U.F.-S., J.D.), Jagiellonian University, Krakow, Poland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Potulska-Chromik","sequence":"additional","affiliation":[{"name":"Department of Neurology, Medical University of Warsaw, Poland (A.P.-C., 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