State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College.
State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College.
Cardiovasc Pathol. 2018 Sep-Oct;36:64-70. doi: 10.1016/j.carpath.2018.07.002. Epub 2018 Jul 26.
Dystrophin gene defects are the pathogenic molecular basis of Becker muscular dystrophy (BMD), characterised by skeletal myopathy and cardiomyopathy. Because of the broad phenotype spectrum, it was difficult to use the traditional diagnostic method to achieve an early accurate diagnosis of BMD-associated cardiomyopathy.
We applied an in-house gene panel testing and a gene-filtering strategy to investigate the genetic defect in a four-generation family with 73 members. The proband had a heart transplant due to heart failure; the explanted heart was subjected to a careful pathological analysis.
A novel small in-frame mutation (c.4998_5000 del CAG, p.1667 del Ala) of the dystrophin gene was identified and co-segregated in the affected family members. By using the image segmentation technology, we found the left ventricular free wall demonstrated severe fibrofatty replacement of cardiac myocytes from the epicardium to the endocardium.
We identified a novel dystrophin mutation (p.1667 del Ala), resulting in BMD-associated cardiomyopathy that demonstrated the pathological features of significant fibrofatty replacement in the sub-epicardial layer of the ventricle; further, the high-throughput sequencing is helpful for making an early diagnosis of BMD.
抗肌萎缩蛋白基因缺陷是 Becker 型肌营养不良症（BMD）的致病分子基础，其特征为骨骼肌病和心肌病。由于表型谱广泛，使用传统的诊断方法很难对 BMD 相关的心肌病进行早期准确诊断。
我们应用内部基因面板检测和基因过滤策略，对一个四代共 73 人的家族中的遗传缺陷进行了研究。先证者因心力衰竭接受了心脏移植；对移植的心脏进行了仔细的病理分析。
在受影响的家族成员中发现了一种新的小型框内缺失突变（c.4998_5000delCAG，p.1667delAla），与疾病共分离。通过使用图像分割技术，我们发现左心室游离壁从心外膜到心内膜表现出心肌细胞的严重纤维脂肪替代。
我们发现了一种新的抗肌萎缩蛋白突变（p.1667delAla），导致 BMD 相关的心肌病，表现为心室心外膜下层明显纤维脂肪替代的病理特征；此外，高通量测序有助于对 BMD 进行早期诊断。
