This study investigates FLNC mutations in Chinese cardiomyopathy patients. Background: Inherited cardiomyopathies, including dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM), restrictive cardiomyopathy (RCM), and arrhythmogenic right ventricular cardiomyopathy (ARVC) are major heart failure causes. FLNC, critical for muscle structure, is implicated in myofibrillar myopathy and isolated DCM (3–4% cases) with ventricular arrhythmias. Missense variants are linked to HCM and protein aggregation. A cohort of 25 patients with pathogenic/likely pathogenic FLNC mutations (2022–2025, Beijing Anzhen Hospital) underwent whole-exome sequencing (WES) using IDT kit 1.0/Hiseq 4000. Variants were classified via the American College of Medical Genetics and Genomics (ACMG) guidelines. Clinical data (echocardiography, CMR, labs) and follow-up data (prognosis, meds, and family history) were collected. The statistics used SPSS (p < 0.05). The mean age was 38 ± 14.6 years (13 males). There were 25 FLNC mutations: 12 single nucleotide polymorphisms (SNPs), 5 deletions, 2 duplications, and 3 deletion-insertions, classified as 6 pathogenic, 16 likely pathogenic, and 3 variants of uncertain significance (VUS). Diagnoses: 24% dilated cardiomyopathy (DCM), 8% hypertrophic cardiomyopathy (HCM), and 4% left ventricular non-compaction. Nonsense mutation carriers exhibited significantly higher tricuspid regurgitation prevalence compared to frameshift mutation carriers (6/9 vs. 2/10; p = 0.04). Echocardiography revealed reduced left ventricular ejection fraction (LVEF) (41.5 ± 14.1%), with statistically significant differences in fractional shortening (p = 0.024) and aortic root diameter (p = 0.028). Pedigree analysis confirmed that a frameshift mutation (LP) co-segregated with familial DCM and was associated with severe phenotypes, including sudden cardiac death. Furthermore, nonsense FLNC mutations correlated with increased tricuspid regurgitation severity, smaller aortic root dimensions, and reduced pulmonary artery flow velocity.

This study examines pediatric cardiomyopathies by analyzing genetic and clinical data from 55 patients (2021–2024) at Beijing Anzhen Hospital. Four subtypes were studied: dilated (DCM, 24), hypertrophic (HCM, 22), arrhythmogenic right ventricular (ARVC, 7), and restrictive (RCM, 2). Clinical data, imaging, labs, and family histories were collected, with whole-exome sequencing (WES) identifying disease-causing variants classified via ACMG guidelines. Statistical analysis revealed a median age of 11 years, a proportion of 58% male participants, and ethnic diversity (21 northern Han, 29 southern Han, 5 minorities). In the cohort, 13 cases had an LVEF below 35%. Pathogenic/likely pathogenic (P/LP) variants were found in 21.8% of the patients, and variants of uncertain significance (VUS) were present in 38.2%, with MYH7 (seven cases) and MYBPC3 (five) being the most common. The WES positivity rates varied, at 58.3% (DCM), 72.7% (HCM), and 33.3% (ARVC/RCM). DCM patients with P/LP/VUS variants showed better contractile function (Fractional Shortening: 29.0% vs. 16.5%, p = 0.008). Females in the DCM group had poorer cardiac function (lower LVEF, higher LVESd, lower cardiac output) compared to males, with more females (nine vs. three) exhibiting an LVEF < 35% (p = 0.041). No significant gender differences were observed in the HCM cases. These findings highlight genotype–phenotype correlations and underscore the need for early intervention in female DCM patients.