The aim of this study was to analyze patients from two distinct families with a novel distal titinopathy phenotype associated with exactly the same CNV in the TTN gene. We used an integrated strategy combining deep phenotyping and complete molecular analyses in patients. The CNV is the most proximal out-of-frame TTN variant reported and leads to aberrant splicing transcripts leading to a frameshift. In this case, the dominant effect would be due to dominant-negative and/or haploinsufficiency. Few CNV in TTN have been reported to date. Our data represent a novel phenotype–genotype association and provides hypotheses for its dominant effects.

中文翻译：

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与拷贝数变异相关的新型显性远端肌腱病表型

本研究的目的是分析来自两个不同家族的患者，这些患者具有与TTN基因中完全相同的 CNV 相关的新型远端肌腱病表型。我们使用了一种综合策略，结合了患者的深度表型分析和完整的分子分析。CNV 是报道的最接近的帧外TTN变体，并导致异常剪接转录本导致移码。在这种情况下，显性效应将是由于显性负和/或单倍体不足。迄今为止，很少有TTN中的CNV报道。我们的数据代表了一种新的表型-基因型关联，并为其主要影响提供了假设。