Related Experiment Video
Updated: Jan 17, 2026
Characterizing Exon Skipping Efficiency in DMD Patient Samples in Clinical Trials of Antisense Oligonucleotides
Published on: May 7, 2020
A novel partial mRNA-derived duplication of the DMD gene identified in NGS carrier screening
Xue Zhang1, Gang Wang, Yuan Wan
1Department of Obstetrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, People's Republic of China. drlu@fudan.edu.cn.
Abstract:
Duplications in the dystrophin gene (DMD) represent a common genetic variation associated with the onset of Duchenne and Becker muscular dystrophy. In this study, we reported a novel mRNA-derived DMD duplication identified by next-generation sequencing (NGS)-based expanded carrier screening (ECS) in a pregnant woman, which was not accurately detected by multiplex ligation probe amplification (MLPA) testing. The discrepancy was elucidated through the analysis of the duplication breakpoint via additional validation experiments. This variation was confirmed to originate from a partially reverse-transcribed intronless cDNA copy of a rare DMD gene transcript mRNA and reinserted into a noncoding region of chromosome 13. The variation was classified as benign because the DMD gene remained intact. We strongly recommend analysing the breakpoints before the pathogenicity assessment of DMD duplication variations, identified in ECS to improve the accuracy of clinical prediction and genetic counselling.
Insights
A novel dystrophin gene (DMD) duplication, found via next-generation sequencing expanded carrier screening, was confirmed to be benign. This mRNA-derived variation highlights the need for breakpoint analysis in DMD duplications for accurate genetic counseling.
Area of Science:
- Genetics
- Molecular Biology
- Medical Diagnostics
Background:
- Dystrophin gene (DMD) duplications are common causes of Duchenne and Becker muscular dystrophy.
- Next-generation sequencing (NGS)-based expanded carrier screening (ECS) is increasingly used for genetic analysis.
- Multiplex ligation probe amplification (MLPA) is a standard method for detecting gene copy number variations.
Purpose of the Study:
- To report a novel mRNA-derived DMD duplication identified by NGS-based ECS.
- To investigate a discrepancy between NGS and MLPA testing for DMD duplication.
- To elucidate the origin and pathogenicity of the identified DMD duplication.
Main Methods:
- Next-generation sequencing (NGS) for expanded carrier screening (ECS).
- Multiplex ligation probe amplification (MLPA) for copy number variation detection.
- Breakpoint analysis using additional validation experiments.
Main Results:
- A novel mRNA-derived DMD duplication was identified in a pregnant woman via NGS-ECS.
- MLPA testing failed to accurately detect this specific DMD duplication.
- Breakpoint analysis revealed the variation originated from a reverse-transcribed intronless DMD mRNA copy reinserted into chromosome 13.
- The DMD gene remained intact, classifying the variation as benign.
Conclusions:
- Breakpoint analysis is crucial for accurate pathogenicity assessment of DMD duplications identified by ECS.
- Novel DMD variations can arise from complex mechanisms like reverse transcription and reinsertion.
- Improved diagnostic accuracy for DMD variations enhances clinical prediction and genetic counseling.
More Related Videos
10:30Multi-exon Skipping Using Cocktail Antisense Oligonucleotides in the Canine X-linked Muscular Dystrophy
Published on: May 24, 2016
08:22A Novel Strategy Combining Array-CGH, Whole-exome Sequencing and In Utero Electroporation in Rodents to Identify Causative Genes for Brain Malformations
Published on: December 1, 2017
