A comparative analysis of long-read sequencing techniques in two neuromuscular diseases

In collaboration with their Japanese colleagues, researchers from the Myology Institute* compared the diagnostic use of new sequencing technologies in the context of a growing number of genetic diseases involving nucleotide expansions:

• first-generation NGS (next-generation sequencing) is unable to measure these pathological expansions, particularly in patients with myotonic dystrophy type 1 (DM1) or oculopharyngeal-distal muscular dystrophy (OPDM),
• this difficulty can be overcome by using long-read sequencing available on machines such as Nanopore coupled with a CRISPR/Cas9 system,
• the DNA of four patients with DM1 and five with OPDM was used as substrate for the study.

This work has helped to refine the mechanisms involved in these two pathologies, in particular the presence of somatic mosaics or areas of hypermethylation.

 

Benarroch L, Boëlle PY, Madry H, Mohand Oumoussa B, Eura N, Nishino I, Labrèche K, Gorbunova V, Bassez G, Stojkovic T, Gourdon G, Bonne G, Tomé S. Comparative Analysis of CRISPR/Cas9-targeted Nanopore Sequencing Approaches in Repeat Expansion Disorders. Genomics Proteomics Bioinformatics. 2025 Oct 22:qzaf094. doi: 10.1093/gpbjnl/qzaf094. Epub ahead of print. PMID: 41131788.

 

* L. Bennarroch, V. Gorbunova and G. Bonne work in the Genetics and pathophysiology of neuromuscular disorders linked to the extracellular matrix and to the nucleus team within the Center of Research in Myology
G. Bassez and T. Stojkovic work in the Nord-Est/Ile-de-France Neuromuscular Disease Reference Centre
G. Gourdon and S. Tomé work in the Repeat Expansions & Myotonic Dystrophy (REDs) team within the Center of Research in Myology