Pediatric Research Institute, Children's Hospital Affiliated to Shandong University (Jinan Children's Hospital), Jinan, China.
Shandong Provincial Clinical Research Center for Children's Health and Disease, Jinan, China.
Hum Genomics. 2024 Oct 29;18(1):118. doi: 10.1186/s40246-024-00683-9.
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.
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.
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.
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.
FLNC 基因突变主要在伴有心肌病的成年人群中报道，而早发病例较为少见。基因型-表型关系表明，扩张型心肌病（DCM）常与 FLNC 截断变异相关。
我们使用下一代测序（NGS）对伴有心血管疾病的患者进行了全面的遗传分析，以鉴定 FLNC 变异。对详细的表型和变异进行分析，以描述临床特征和遗传改变。使用迷你基因检测和结构建模来研究鉴定变异引起的致病性。
在 58 名患者的队列中，分别在患有扩张型和混合限制/肥厚型心肌病的患者中发现了新型杂合 FLNC 变体 c.3962A>T（p.Glu1321Val）和 c.7543C>T（p.Leu2515Phe）。c.3962A>T 变体通过剪接预测工具和迷你基因研究显示出正常剪接的破坏，进一步强调了其潜在的致病性。
对于 DCM 患者的 FLNC 错义变异，应仔细检查变异的剪接效果。鉴于发生心脏性猝死和严重心脏并发症的风险较高，早期发现和干预至关重要。
