基于MLPA的NGS在DMD和SMA CNV致病机制检测中的应用

Application of a Multiplex Ligation‑Dependent Probe Amplification‑Based Next‑Generation Sequencing Approach for the Detection of Pathogenesis of Duchenne Muscular Dystrophy and Spinal Muscular Atrophy Caused by Copy Number Aberrations

Yongchen Yang1  · Chaoran Xia2 · Xiaozhen Song1 · Xiaojun Tang1 · Xueling Nie3 · Wuhen Xu1 · Chengkan Du1 · Hong Zhang1 · Peng Luo2

• PMID： 37596438

• PMCID： PMC10791777

• DOI： 10.1007/s12035-023-03572-9

Abstract

Both Duchenne muscular dystrophy (DMD; OMIM no. 310200) and spinal muscular atrophy (SMA; OMIM no. 253300/253550/253400/271150) are genetic disorders characterized by progressive muscle degeneration and weakness. Genetic copy number aberrations in the pathogenetic genes DMD and SMN1 lead to alterations in functional proteins, resulting in DMD and SMA, respectively. Multiplex ligation-dependent probe amplification (MLPA) has become a standard method for the detection of common copy number aberrations (CNAs), including DMD and SMN1 deletions, both of which are associated with poor clinical outcomes. However, traditional MLPA assays only accommodate a maximum of 60 MLPA probes per test. To increase the number of targeted sequences in one assay, an MLPA-based next-generation sequencing (NGS) assay has been developed that is based on the standard MLPA procedure, allows high-throughput screening for a large number of fragments and samples by integrating additional indices for detection, and can be analyzed on all Illumina NGS platforms.

Keywords Duchenne muscular dystrophy (DMD) · Spinal muscular atrophy (SMA) · Multiplex ligation-dependent probe amplification (MLPA) · Copy number aberrations (CNAs) · Next-generation sequencing (NGS)