Song Danyu, Li Xiaomei, Wei Wei, Liu Xueqin, Wu Lin, Xiong Hui
Department of Pediatrics, Peking University First Hospital, Beijing, China.
Department of Pediatric Cardiology, The First Hospital of Tsinghua University (Beijing Huaxin Hospital), Beijing, China.
Front Genet. 2021 Dec 17;12:786294. doi: 10.3389/fgene.2021.786294. eCollection 2021.
Emery-Dreifuss muscular dystrophy (EDMD) is a rare disease characterized by early joint contractures, slowly progressive muscular dystrophy, and cardiac involvement, which includes arrhythmia, dilated cardiomyopathy, hypertrophic cardiomyopathy, heart failure, and sudden death. Clinical data of the proband and family members were collected. The next-generation sequencing technology was used to analyze the pathogenic variants and copy number variations. Polymerase chain reaction was used to sequence the breakpoints of gene locus rearrangements. Here, we report two siblings with EDMD in a family. The proband, a 17-year-old boy, manifested a dilated right heart, bradycardia, mild muscle weakness, and joint contractures. His younger brother only showed a mild bowing limitation with elevated creatine kinase. Next-generation sequencing revealed the complete deletion of and a rearrangement in (exon29_48dup) in these two patients. The deletion and partial duplication were accompanied by a 5 bp overlap (GTCCC) on the background of the inversion. These findings support the pathogenic mechanism of microhomology-mediated nonhomologous end joining. We report two siblings with complete deletion and duplication in a family. A microhomology-mediated nonhomologous end joining event involving and acts as the underlying mechanism.
埃默里-德赖富斯肌营养不良症（EDMD）是一种罕见疾病，其特征为早期关节挛缩、缓慢进展的肌营养不良以及心脏受累，包括心律失常、扩张型心肌病、肥厚型心肌病、心力衰竭和猝死。收集了先证者及其家庭成员的临床数据。采用二代测序技术分析致病变异和拷贝数变异。利用聚合酶链反应对基因座重排的断点进行测序。在此，我们报告一个家族中有两名患有EDMD的兄弟姐妹。先证者是一名17岁男孩，表现为右心扩张、心动过缓、轻度肌无力和关节挛缩。他的弟弟仅表现出轻度的脊柱前凸受限，肌酸激酶升高。二代测序显示这两名患者存在 的完全缺失以及 （外显子29_48dup）的重排。 的缺失和 的部分重复在 倒位的背景下伴有5个碱基对的重叠（GTCCC）。这些发现支持了微同源性介导的非同源末端连接的致病机制。我们报告一个家族中有两名兄弟姐妹存在 的完全缺失和 的重复。涉及 和 的微同源性介导的非同源末端连接事件是潜在机制。
