{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:12:02Z","timestamp":1787026322271,"version":"build-2736575974"},"reference-count":13,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T00:00:00Z","timestamp":1762819200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cardiovasc. Med."],"abstract":"<jats:p>An estimated 30%\u201350% of dilated cardiomyopathy (DCM) cases are attributable to genetic factors, with titin (TTN) mutations constituting the most prevalent genetic etiology, accounting for 20%\u201325% of hereditary DCM cases. The majority of pathogenic TTN variants are heterozygous truncating mutations (TTNtv), including frameshift, nonsense, and canonical splice-site variants. Alport syndrome (AS) represents the second most common monogenic cause of end-stage kidney disease (ESKD). While COL4A5 gene variants cause X-linked AS, mutations in COL4A3 or COL4A4 genes (both located on chromosome 2) are associated with autosomal recessive AS, autosomal dominant AS, and thin basement membrane nephropathy. We present a unique case featuring both a novel TTN variant and a rare COL4A4 mutation in a DCM patient. This dual rare variant presentation is clinically exceptional and may contribute to expanding the genetic landscape of DCM and informing future investigations into genotype-phenotype correlations between TTN mutations and DCM pathogenesis.<\/jats:p>","DOI":"10.3389\/fcvm.2025.1668842","type":"journal-article","created":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T06:31:13Z","timestamp":1762842673000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Case Report: A novel TTN gene variant and a concurrent rare COL4A4 gene variant in a Chinese patient with dilated cardiomyopathy"],"prefix":"10.3389","volume":"12","author":[{"given":"Shan","family":"Han","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying-Yi","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Geng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,11,11]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"3599","DOI":"10.1093\/eurheartj\/ehab368","article-title":"2021 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure","volume":"42","author":"McDonagh","year":"2021","journal-title":"Eur Heart J"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1288328","DOI":"10.3389\/fcvm.2023.1288328.eCollection","article-title":"Case report: a new de novo mutation of the troponin T2 gene in a Chinese 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