Fig. 5: Spliceosome components are downregulated in strongly affected FSHD patients (group 4).

a Splicing factors and splicing regulators are downregulated in FSHD. b The downregulation of spliceosome components leads to increased exon skipping (ES) events in FSHD. In controls, many intron retentions (IR) events are found that are not present in FSHD patients. However, ~75% of these intron exclusion events in FSHD have actually skipped exons, which naturally include adjacent introns. Around 25% of introns are spliced out although retained in controls, while there are also intron retention events in FSHD patients that are not present in controls (pie chart). The amount of alternative splice site usage (3’ Alt3, 5’ Alt5) is slightly reduced in FSHD patients. c All genes with differentially used splicing events were used for a GO term enrichment analysis, showing that these genes contribute to the known FSHD phenotype. d Heatmap of selected genes with alternative splice site usage; colour indicates Ψ-values (percent spliced in), and all events have at least an absolute ΔΨ-value of 0.1 between controls and FSHD patients. e Exon skipping (ES) and intron retention (IR) events are differentially used in FSHD patients. Reference exons are indicated in yellow and colored lines show the possible local splicing variations. Bars show proportional usage of event usage in controls and FSHD patients; violin plots display Ψ-values of the respective local splicing variations.