The clinical application of a sequencing technique in Steinert disease-like disorders

Researchers from the Center for Research in Myology, in collaboration with national and international researchers, have recently published a review on the clinical application of long-read sequencing (LRS) in diseases associated with expanded repeat sequences, including Steinert’s disease. The authors discuss recent findings from LRS, methodological and bioinformatics advances, as well as emerging diagnostic applications, to illustrate the potential of LRS to transform both research and clinical practice.

The REDs
Repeat expansion disorders (REDs) constitute a group of rare diseases with specific genetic characteristics:

• they are caused by an abnormal increase in the number of repeats (expansions) of short DNAmacromolécule complexe, l’ADN est le support de l’hérédité (gènes). C’est le constituant des chromosomes. L’ADN est organisé en double hélice (deux brins complémentaires) et constitué de nucléotides de quatre types : adénine, guanine, cytosine et thymine. sequences, known as STRs (Short Tandem Repeat),
• these expansions can exceed several kilobases and exhibit a complex structure, variations in size between cells within the same individual (somatic instability), the presence of other DNA sequences within the expansion (interruptions) and methylation specific to certain alleles.

These characteristics are essential for understanding the mechanisms of the disease, clinical variability, prognosis and, potentially, clinical decision-making. However, traditional diagnostic methods do not allow them to be characterised accurately.

The value of LRS
Long-read sequencing enables the complexity of STRs to be studied in detail in a single test. It facilitates the discovery of new pathogenic repeat expansions and promotes advances in diagnostics, clinical research and basic research.