{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T18:11:18Z","timestamp":1780337478792,"version":"3.54.1"},"reference-count":44,"publisher":"American Society for Clinical Investigation","issue":"11","license":[{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,6,1]]},"abstract":"<jats:p>\n                    Dilated cardiomyopathy (DCM) is a genetically heterogeneous disorder, characterized by ventricular dilatation and impaired systolic function, leading to heart failure and sudden cardiac death. Despite advances in genomic technologies, the genetic cause of DCM remains unidentified in more than half of the cases. Here, we performed an integrative analysis of genomic and transcriptomic data from patient-derived cardiac tissue to identify causative variants in genetically undiagnosed DCM. This approach enabled us to identify a homozygous splice-site variant (c.243+6T&gt;A) in the sarcoglycan gene\n                    <jats:italic>SGCB<\/jats:italic>\n                    , which results in exon 2 skipping. This variant was significantly enriched in patients with DCM compared with the general population, with consistent genotype\u2013phenotype correlations observed across multiple families. Protein-level analysis of cardiac tissue from homozygous individuals revealed loss of \u03b2-sarcoglycan, the protein product of\n                    <jats:italic>SGCB<\/jats:italic>\n                    , and destabilization of the sarcoglycan complex. Although\n                    <jats:italic>SGCB<\/jats:italic>\n                    has been previously associated with limb-girdle muscular dystrophy, these homozygous individuals showed no biochemical or clinical signs of skeletal muscle involvement, indicating an absence of myopathy. Compared with variant-negative patients with DCM, homozygous individuals also had a higher risk of early-onset adverse cardiac events. Together, these findings identify c.243+6T&gt;A in\n                    <jats:italic>SGCB<\/jats:italic>\n                    as a cause of isolated DCM associated with unfavorable clinical outcomes.\n                  <\/jats:p>","DOI":"10.1172\/jci198675","type":"journal-article","created":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T17:44:46Z","timestamp":1780335886000},"source":"Crossref","is-referenced-by-count":0,"title":["Homozygous SGCB splice-site variant causes isolated dilated cardiomyopathy through sarcoglycan complex destabilization in East Asians"],"prefix":"10.1172","volume":"136","author":[{"given":"Fangfang","family":"Li","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Medicine, The University of Osaka Graduate School of Medicine, Osaka, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haruki","family":"Shinomiya","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, The University of Osaka Graduate School of Medicine, Osaka, Japan."},{"name":"Department of Genomic Medicine and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7368-3584","authenticated-orcid":true,"given":"Yuki","family":"Kuramoto","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, The University of Osaka Graduate School of Medicine, Osaka, Japan."},{"name":"Department of Pathophysiology of Heart Failure and Therapeutics, National Cerebral and Cardiovascular Center Research Institute, Osaka, Japan."},{"name":"Premium Research Institute for Human Metaverse Medicine (WPI-PRIMe), The University of Osaka, Osaka, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koshiro","family":"Kanaoka","sequence":"additional","affiliation":[{"name":"Department of Medical and Health Information Management, National Cerebral and Cardiovascular Center Research Institute, Osaka, 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