Background

Filamin C is a cytoskeletal protein expressed in cardiac cells. Nonsense variations in the filamin C gene (FLNC) were associated with dilated and arrhythmogenic cardiomyopathies.

Methods and results

We identified an intronic variation in FLNC gene (c.3791-1G > C) in three unrelated Ashkenazi Jewish families with variable expression of arrhythmia and cardiomyopathy. cDNA was prepared from a mutation carrier's cultured skin fibroblasts. Quantitative PCR demonstrated a reduction in total FLNC transcript, and no other FLNC splice variants were found. Single-nucleotide polymorphism (SNP) analysis revealed heterozygous variations in the genomic DNA that were not expressed in the messenger RNA. Immunohistochemical analysis of cardiac sections detected a normal distribution of filamin C protein in the heart ventricles.

Conclusion

The transcript that included the FLNC variant was degraded. Haploinsufficiency in filamin C underlies arrhythmogenic cardiomyopathy with variable symptoms.

中文翻译：

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细丝蛋白 C 转录物的减少与德系犹太人的致心律失常性心肌病有关。

背景

细丝蛋白 C 是一种在心肌细胞中表达的细胞骨架蛋白。细丝蛋白 C 基因 ( FLNC ) 的无意义变异与扩张型和致心律失常性心肌病有关。

方法和结果

我们在三个不相关的德系犹太人家庭中发现了FLNC基因 (c.3791-1G > C) 的内含子变异，其心律失常和心肌病的表达各不相同。从突变载体培养的皮肤成纤维细胞制备cDNA。定量 PCR 显示总FLNC转录物减少，并且没有发现其他FLNC剪接变体。单核苷酸多态性 (SNP) 分析揭示了基因组 DNA 中未在信使 RNA 中表达的杂合变异。心脏切片的免疫组织化学分析检测到心室中细丝蛋白 C 蛋白的正常分布。

结论

包含FLNC变体的转录本被降解。细丝蛋白 C 的单倍体不足是具有不同症状的致心律失常性心肌病的基础。