小儿心肌病中的新型 FLNC 变异:对疾病机理的深入了解。

IF 3.8 3区 医学 Q2 GENETICS & HEREDITY Human Genomics Pub Date : 2024-10-29 DOI:10.1186/s40246-024-00683-9
Rui Dong, Xin Zhou, Haiyan Zhang, Bingyi Shi, Guohua Liu, Yi Liu
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引用次数: 0

摘要

背景:FLNC基因变异主要见于成年心肌病患者,而早发病例较少见。基因型与表型的关系表明,扩张型心肌病(DCM)通常与 FLNC 截断变异有关:我们利用新一代测序技术(NGS)进行了全面的遗传分析,以确定心血管疾病患者的 FLNC 变异。我们进行了详细的表型和变异分析,以确定临床特征和基因改变的特点。利用微型基因检测和结构建模研究了所发现变异的致病性:结果:在一组 58 例患者中,发现了新型杂合子 FLNC 变异 c.3962A > T(p.Glu1321Val)和 c.7543C > T(p.Leu2515Phe),它们分别出现在扩张型和限制型/肥厚型混合型心肌病患者中。c.3962A > T变异破坏了正常剪接,剪接预测工具和迷你基因研究证明了这一点,进一步强调了其致病潜力:结论:对于DCM患者中的FLNC错义变异,应仔细检查该变异的剪接效应。鉴于心脏性猝死和严重心脏并发症的高风险,早期发现和干预至关重要。
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Novel FLNC variants in pediatric cardiomyopathy: an insight into disease mechanisms.

Background: FLNC gene variants have predominantly been reported in adult populations with cardiomyopathies, and early-onset cases are less common. The genotype-phenotype relationship indicates that dilated cardiomyopathy (DCM) is often associated with FLNC truncating variants.

Methods: We conducted a comprehensive genetic analysis using next generation sequencing (NGS) to identify FLNC variants in patients with cardiovascular conditions. Detailed phenotypic and variant analyses were performed to characterize the clinical features and genetic alterations. Minigene assays and structural modeling were used to investigate the pathogenicity caused by the identified variants.

Results: In a cohort of 58 patients, novel heterozygous FLNC variants, c.3962A > T (p.Glu1321Val) and c.7543C > T (p.Leu2515Phe), were identified in patients presenting with dilated and mixed restrictive/hypertrophic cardiomyopathies, respectively. The c.3962A > T variant disrupted normal splicing, as demonstrated through the splicing prediction tool and minigene studies, further emphasizing its pathogenic potential.

Conclusion: For missense variants of FLNC in patients with DCM, the splicing effect of the variant should be carefully checked. Early detection and intervention are crucial given the high risk of sudden cardiac death and severe cardiac complications.

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来源期刊
Human Genomics
Human Genomics GENETICS & HEREDITY-
CiteScore
6.00
自引率
2.20%
发文量
55
审稿时长
11 weeks
期刊介绍: Human Genomics is a peer-reviewed, open access, online journal that focuses on the application of genomic analysis in all aspects of human health and disease, as well as genomic analysis of drug efficacy and safety, and comparative genomics. Topics covered by the journal include, but are not limited to: pharmacogenomics, genome-wide association studies, genome-wide sequencing, exome sequencing, next-generation deep-sequencing, functional genomics, epigenomics, translational genomics, expression profiling, proteomics, bioinformatics, animal models, statistical genetics, genetic epidemiology, human population genetics and comparative genomics.
期刊最新文献
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