Practical Recommendations for the Selection of Patients for Individualized Splice-Switching ASO-Based Treatments

Figure 4

Variant 1—canonical splice site variant. Pathogenic variants that destroy or severely weaken the 5 donor or 3 acceptor sites often result in intron retention (cryptic exon) or (partial) exon skipping. This can lead to disruption of the reading frame of the transcript and reduced protein production. As the splicing machinery cannot recognize destroyed splice sites, normal splicing cannot be restored with an ASO. The shape of the exon indicates the reading frame, and grey marked areas are protein domains. ss: splice site.