Microhomology-Mediated Nonhomologous End Joining Caused Rearrangement of and in Emery-Dreifuss Muscular Dystrophy.

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.