Case report: A Novel TTN Gene Variant and a Concurrent Rare COL4A4 Gene Variant in a Chinese Patient with Dilated Cardiomyopathy

Shan HanYing-Yi Zhang^*Jie Geng^*

• Tianjin Chest Hospital, Tianjin, China

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.