Point mutation R723G in the MYH7 gene causes hypertrophic cardiomyopathy (HCM). Heterozygous patients with this mutation exhibit a comparable allelic imbalance of the MYH7 gene. On average 67% of the total MYH7 mRNA are derived from the MYH7R723G-allele and 33% from the MYH7WT allele. Mechanisms underlying mRNA allelic imbalance are largely unknown. We suggest that a different mRNA lifetime of the alleles may cause the allelic drift in R723G patients. A potent regulator of mRNA lifetime is its secondary structure. To test for alterations in the MYH7R723G mRNA structure we used selective 2'-hydroxyl acylation analyzed by primer extension (SHAPE) analysis. We show significantly different SHAPE reactivity of wild-type and MYH7R723G RNA, which is in accordance with bioinformatically predicted structures. Thus, we provide the first experimental evidence for mRNA secondary structure alterations by the HCM point mutation. We assume that this may result in a prolonged lifetime of MYH7R723G mRNA in vivo and subsequently in the determined allelic imbalance.

中文翻译：

---

肥厚型心肌病MYH7突变R723G改变了mRNA的二级结构。

MYH7基因中的点突变R723G导致肥厚型心肌病（HCM）。具有这种突变的杂合子患者表现出可比的MYH7基因等位基因失衡。平均而言，平均MYH7 mRNA的67％来自MYH7R723G等位基因，而33％来自MYH7WT等位基因。mRNA等位基因失衡的基本机制尚不清楚。我们建议等位基因的不同mRNA寿命可能会导致R723G患者的等位基因漂移。mRNA寿命的有效调节剂是其二级结构。为了测试MYH7R723G mRNA结构的变化，我们使用了通过引物延伸（SHAPE）分析法进行的选择性2'-羟基酰化反应。我们显示野生型和MYH7R723G RNA的SHAPE反应性显着不同，这与生物信息学预测的结构一致。从而，我们提供了第一个通过HCM点突变进行mRNA二级结构改变的实验证据。我们假设这可能导致MYH7R723G mRNA的体内寿命延长，并随后导致确定的等位基因失衡。