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Updated: Apr 26, 2026
Characterizing Exon Skipping Efficiency in DMD Patient Samples in Clinical Trials of Antisense Oligonucleotides
Published on: May 7, 2020
Exome sequencing as a second-tier diagnostic approach for clinically suspected dysferlinopathy patients
Marc Bartoli1, Jean-Pierre Desvignes, Levy Nicolas
1Aix Marseille Université, INSERM, GMGF, UMR_S 910, 13385, Marseille, France; APHM, Département de Génétique Médicale, Hôpital Timone Enfants, Marseille, 13385, France.
Introduction:
Autosomal recessive muscular dystrophies are heterogeneous genetic disorders, with 39 genes currently implicated. Genetic diagnosis using targeted single-gene analysis by Sanger sequencing yields negative results in 10-20% of samples, warranting clinical re-evaluation and time-consuming testing of additional genes. This applies to dysferlinopathies caused by mutations in the gene encoding dysferlin (DYSF), which presents mainly as limb-girdle muscular dystrophy (LGMD) or distal myopathy.
Methods:
We evaluated exome sequencing associated with data filtering for selected genes as a second-tier approach for genetic diagnosis in a cohort of 37 patients with an initial negative result on targeted DYSF analysis.
Results:
Exome sequencing allowed for establishing (16%) or suggesting (8%) the molecular diagnosis by implicating other known LGMD or distal myopathy genes or by revealing DYSF mutations previously missed using mutation-screening techniques with incomplete detection yields.
Conclusions:
Exome sequencing associated with data filtering constitutes an efficient second-tier analysis for genes implicated in LGMD or distal myopathies.
