Table 1.
Summary of splicing-related diseases that might be target for gene therapy.
| Disease | Regulatory Element Mutated | Mechanism | Splicing Effect | References | |
|---|---|---|---|---|---|
| Familial dysautonomia (FD) | Cis | T > C mutation at position 6 of intron 20 of the IKBKAP gene | Exon skipping; introduction of a premature termination codon (PTC) | [23] | |
| Spinal muscular atrophy (SMA) | Cis | C > T mutation at position 6 of exon 7 of the SMN2 gene | Alteration of a putative ESE | [24] | |
| Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency | Cis | c362C > T mutation in exon 5 of the MCAD gene | Exon skipping | [25] | |
| Hutchinson-Gilford progeria syndrome (HGPS) | Cis | c1824C > T mutation in exon 11 of LMNA gene | Activation of a cryptic splice site | [26] | |
| Myotonic dystrophy | Type 1 (DM1) | Cis | Expanded CTG tract in the 3′ UTR region of the DMPK gene | Misregulation of trans-acting factors | [27] |
| Type 2 (DM2) | Cis | Expanded CCCTG tract in intron 1 of the ZNF9 gene | Misregulation of trans-acting factors | [27] | |
| Autosomal dominant retinitis pigmentosa (RP) | Trans | Mutations in genes of the core spliceosome (PRPF31, PRPF8, PRPF3, RP9) | Disruption of basal spliceosome function | [28] | |
| Duchenne muscular dystrophy (DMD) | Cis | T > A mutation in exon 31 of the Distrophin gene | Creation of a PTC and introduction of ESS | [29] | |
| Microcephalic steodysplastic primordial dwarfism type 1 (MOPD1) or Taybi-Linder syndrome (TALS) | Trans | Mutations in the gene encoding the U4atac snRNA | Reduced splicing efficiency and increased intron retention | [30] | |
| Frontotemporal dementia with parkinsonism-17 (FTDP-17) | Cis | Mutations within and downstream exon 10 of the MAPT gene | Disruption of Tau protein balance | [31] | |
| Fukuyama congenital muscular dystrophy (FCMD) | Cis | SVA insertion in the 3′ UTR of the FKTN gene | Inclusion of a new exon | [32] | |
| Amyotrophic lateral sclerosis (ALS) | Trans | Mutations in TDP-43 | Altered gene splicing | [33] | |
| Hypercholesterolemia | Cis | rs688T > C mutation in exon 12 of the LDLR gene | Alteration of ESE and exon skipping | [34] | |
| Cystic fibrosis (CF) | Cis | Longer (UG)n tract at the exon 9 3′ SS of the CFTR gene | Exon skipping | [35] | |