Long-read genomic and epigenomic profiling enhances timely comprehensive variant discovery in hypotonia and muscle weakness

Hypotonia (decreased muscle tone) is a key symptom in many disorders, but it has diverse genetic causes so can require multiple tests to obtain a genetic diagnosis. Short-read sequencing often fails to uncover the underlying variant as it cannot detect complex structural variants, repeat expansions, or epigenetic modifications. In this study, Abuijlan et al. used Oxford Nanopore sequencing to successfully identify all known pathogenic variants in a reference cohort, revealing the causative variants in previously unsolved cases. This single-test approach demonstrated strong potential to streamline and accelerate rare disease identification in the future.

Sample type: genomic DNA from whole blood

Kit: Ligation Sequencing Kit