Table 2.
Characteristics of PLP1 gene mutations identified in 14 unrelated patients and MutPred analysis of the missense mutations
| Location | cDNA mutation* | Mutation Effect | MutPred analysis of missense mutations | Refer ence | |||||
|---|---|---|---|---|---|---|---|---|---|
| Probability of deleterious mutation |
No. of ESE binding sites loses | No. of ESS binding sites gained | Skippy Log Odds Ratio (LOR) Total | Splice site disruption prediction | |||||
| 5'UTR-Ex 1-Intr 1 | c.1-329_c.1_c.4 +324del657 | r.? | . | . | . | . | Present study | ||
| c.134_140dup7 | p.Ile47IlefsX4 | . | . | . | . | Present study | |||
| Exon 2 | c.83G>T | p.Gly28Val | 0.80 | SS Loss of loop (P = 0.0252) |
0 | 1 | 0.052 | Present study | |
| c.89C>A | p.Ala30Glu | 0.84 | 0 | 0 | -5.884 | Present study | |||
| c.205C>T | p.Gln69X | . | 0 | 2 | 1.290 | Present study | |||
| c.436C>G | p.Leu146Val | 0.67 | 0 | 5 | 0.356 | Present study | |||
| Exon 3 | c.453G>T | p.Lys151Asn | 0.63 | 0 | 0 | -1.284 | [predicted to abolish 5'SS with Neural Network] already reported in the cited ref | Hobson et al. [38] |
|
| c.476T>C | p.Leu159Pro | 0.87 | SS Helix > Sheet (P = 0.0266), Gain of glycosylation at T160 (P = 0.0342) |
6 | 0 | 1.360 | Present study | ||
| Exon 4 | c.505T>C | p.Cys169Arg | 0.91 | 4 | 0 | 1.360 | Mimault et al. [48] |
||
| c.552C>G | p.Cys184Trp | 0.88 | 2 | 0 | -0.929 | Present study | |||
| c.554_564del11 | p.Gln185LeufsX15 | . | Present study | ||||||
| Exon 5 | c.634T>C | p.Trp212Arg | 0.79 | Loss of catalytic residue at L210 (P = 0.0114), Gain of methylation at W212 (P = 0.0245) |
0 | 0 | -1.284 | Cailloux et al. [35] |
|
| c.689C>T | p.Thr230Ile | 0.68 | 5 | 1 | 2.696 | Present study | |||
| Exon 6 | c.740C>A | p.Ala247Asp | 0.88 | 1 | 2 | 2.006 | Present study | ||
* Nucleotide numbers are derived from cDNA PLP1 sequence (GenBank-EMBL accession no. NM_000533.3) taking as nucleotide +1 the A of the first ATG translation initiation codon; Bold type denotes novel mutation; Ex = exon; Intr = Intron; ESE = exonic splicing enhancers; ESS = exonic splicing silencers; Skippy Log Odds Ratio (LOR) score is the output from the Skippy tool [30], the Skippy LOR score represents the likelihood that the combination of ESR changes consequent to a substitution are associated with exon skipping. The higher the Skippy LOR score, the more likely the combination of ESR changes will be associated with an exon skipping event. The prediction of splice site disruption was evaluated using a neural network. The column 'Location' refers to the exon within which the mutation occurs and also the exon that could potentially be skipped due to ESE loss and/or ESS gain.