AUTHOR=Han Shan , Zhang Ying-Yi , Geng Jie 

TITLE=Case Report: A novel TTN gene variant and a concurrent rare COL4A4 gene variant in a Chinese patient with dilated cardiomyopathy

JOURNAL=Frontiers in Cardiovascular Medicine

VOLUME=Volume 12 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2025.1668842

DOI=10.3389/fcvm.2025.1668842

ISSN=2297-055X

ABSTRACT=An estimated 30%–50% of dilated cardiomyopathy (DCM) cases are attributable to genetic factors, with titin (TTN) mutations constituting the most prevalent genetic etiology, accounting for 20%–25% 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.