{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:50:12Z","timestamp":1787028612884,"version":"build-2736575974"},"reference-count":20,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T00:00:00Z","timestamp":1765497600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Science and Technology Innovation Fund-Major Science and Technology Innovation Research and Development Special Project","award":["KCZD202202"],"award-info":[{"award-number":["KCZD202202"]}]},{"name":"Capital\u2019s Funds for Health Improvement and Research","award":["CRF-2024\u20131-2062"],"award-info":[{"award-number":["CRF-2024\u20131-2062"]}]},{"name":"Noncommunicable Chronic Diseases-National Science and Technology Major Project","award":["2023ZD0514400"],"award-info":[{"award-number":["2023ZD0514400"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCDD"],"abstract":"<jats:p>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\u20134% 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\u20132025, 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 &lt; 0.05). The mean age was 38 \u00b1 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 \u00b1 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.<\/jats:p>","DOI":"10.3390\/jcdd12120492","type":"journal-article","created":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T15:52:59Z","timestamp":1765813979000},"page":"492","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Genetic and Clinical Characterization of FLNC Variants in Chinese Patients with Cardiomyopathy"],"prefix":"10.3390","volume":"12","author":[{"given":"Guofeng","family":"Xing","sequence":"first","affiliation":[{"name":"Department of Pediatric Cardiac Surgery, Beijing Anzhen Hospital, Capital Medical University, No.2 Anzhen Street, Chaoyang District, Beijing 100029, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pediatric Cardiology, Beijing Anzhen Hospital, Capital Medical University, No.2 Anzhen Street, Chaoyang District, Beijing 100029, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lizhi","family":"Lv","sequence":"additional","affiliation":[{"name":"Department of Pediatric Cardiac Surgery, Beijing Anzhen Hospital, Capital Medical University, No.2 Anzhen Street, Chaoyang District, Beijing 100029, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengming","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Pediatric Cardiac Surgery, Beijing Anzhen Hospital, Capital Medical University, No.2 Anzhen Street, Chaoyang District, Beijing 100029, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengmei","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pediatric Cardiac Surgery, Beijing Anzhen Hospital, Capital Medical University, No.2 Anzhen Street, Chaoyang District, Beijing 100029, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yabing","family":"Duan","sequence":"additional","affiliation":[{"name":"Department of Pediatric Cardiac Surgery, Beijing Anzhen Hospital, Capital Medical University, No.2 Anzhen Street, Chaoyang District, Beijing 100029, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiachen","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pediatric Cardiac Surgery, Beijing Anzhen Hospital, Capital Medical University, No.2 Anzhen Street, Chaoyang District, Beijing 100029, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pediatric Cardiac Surgery, Beijing Anzhen Hospital, Capital Medical University, No.2 Anzhen Street, Chaoyang District, Beijing 100029, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyan","family":"Li","sequence":"additional","affiliation":[{"name":"Beijing Institution of Heart Lung and Blood Vassal Diseases, Beijing Anzhen Hospital, Capital Medical University, No.2 Anzhen Street, Chaoyang District, Beijing 100029, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1083\/jcb.148.1.115","article-title":"Filamin 2 (FLN2): A muscle-specific sarcoglycan interacting protein","volume":"148","author":"Thompson","year":"2000","journal-title":"J. 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Cardiovasc. Med., 8.","DOI":"10.3389\/fcvm.2021.690846"}],"container-title":["Journal of Cardiovascular Development and Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2308-3425\/12\/12\/492\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T16:15:07Z","timestamp":1765815307000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2308-3425\/12\/12\/492"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,12]]},"references-count":20,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["jcdd12120492"],"URL":"https:\/\/doi.org\/10.3390\/jcdd12120492","relation":{},"ISSN":["2308-3425"],"issn-type":[{"value":"2308-3425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,12]]}}}