Molecular Genetic Analysis of the PLP1 Gene in 38 Families with PLP1-related disorders: Identification and Functional Characterization of 11 Novel PLP1 Mutations

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.

ISSN: 1750-1172