Data from: Cardiac dysfunction in Duchenne muscular dystrophy is less frequent in patients with mutations in the dystrophin Dp116 coding region than in other regions

Background: Duchenne muscular dystrophy (DMD), the most common inherited muscular disease in childhood, is caused by dystrophin deficiency because of mutations in the DMD gene. Although DMD is characterized by fatal progressive muscle wasting, cardiomyopathy is the most important nonmuscle symptom threatening the life of patients with DMD. The relationship between cardiac involvement and dystrophin isoforms has not been analyzed.

Methods and Results: The results of 1109 echocardiograms obtained from 181 Japanese DMD patients with confirmed mutations in the DMD gene were retrospectively analyzed. Patients showed an age-related decline in left ventricular ejection fraction. Patients were divided by patterns of dystrophin isoform deficiency into 5 groups. The cardiac dysfunction-free survival was significantly higher in the group with mutations in the Dp116 coding region than the others, whereas no significant differences in the other 3 groups. At age 25 years, the cardiac dysfunction-free rate was 0.6 in the Dp116 group, but only 0.1 in others. PCR amplification of Dp116 transcript in human cardiac muscle indicated promoter activation.

Conclusions: Left ventricular ejection fraction in DMD declined stepwise with age. Cardiac dysfunction was less frequent in Dp116-deficient than other patients with DMD. Dp116 transcript was identified in human cardiac muscle for the first time. These results indicate that Dp116 is associated with cardiac involvement in DMD.

背景：杜氏肌营养不良症（Duchenne muscular dystrophy, DMD）是儿童期最常见的遗传性肌肉疾病，由DMD基因变异导致肌营养不良蛋白（dystrophin）缺乏引发。尽管DMD以致命性进行性肌肉萎缩为典型特征，但心肌病（cardiomyopathy）是威胁DMD患者生命的最主要非肌肉系统并发症。目前尚未有研究分析心脏受累与肌营养不良蛋白同工型（dystrophin isoforms）之间的关联。
方法与结果：本研究回顾性分析了181例经基因确诊的日本DMD患者的1109次超声心动图（echocardiogram）检查结果。研究对象的左心室射血分数（left ventricular ejection fraction）随年龄增长呈进行性下降趋势。根据肌营养不良蛋白同工型缺乏的模式将患者分为5组。其中，Dp116编码区存在变异的组别，其无心功能障碍生存率显著高于其余组别，而其余3组之间未观察到显著差异。在25岁时，Dp116组的无心功能障碍生存率为0.6，而其余组别仅为0.1。对人类心肌组织中Dp116转录本的聚合酶链反应（polymerase chain reaction, PCR）扩增结果显示，其启动子存在激活现象。
结论：DMD患者的左心室射血分数随年龄呈进行性下降。与其他DMD患者相比，Dp116缺乏者的心功能障碍发生率更低。本研究首次在人类心肌组织中鉴定出Dp116转录本。上述结果表明，Dp116与DMD的心脏受累情况密切相关。