AUTHOR=Song Danyu , Li Xiaomei , Wei Wei , Liu Xueqin , Wu Lin , Xiong Hui 

TITLE=Microhomology-Mediated Nonhomologous End Joining Caused Rearrangement of EMD and FLNA in Emery-Dreifuss Muscular Dystrophy

JOURNAL=Frontiers in Genetics

VOLUME=Volume 12 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2021.786294

DOI=10.3389/fgene.2021.786294

ISSN=1664-8021

ABSTRACT=Background: 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.
Methods: Clinical data of the proband and family members were collected. Next-generation sequencing technology was used to analyse the pathogenic variants and copy number variations. Polymerase chain reaction was used to sequence the breakpoints of gene locus rearrangements.
Results: 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 EMD and a rearrangement in FLNA (exon29_48dup) in these two patients. The EMD deletion and partial FLNA duplication was accompanied by a 5 bp overlap (GTCCC) on the background of the FLNA-EMD inversion. These findings support the pathogenic mechanism of microhomology-mediated nonhomologous end joining.
Conclusion: We report two siblings with complete EMD deletion and FLNA duplication in a family. A microhomology-mediated nonhomologous end joining event involving EMD and FLNA acts as the underlying mechanism.