<i>In silico</i> splice site predictions.

<p>A comprehensive overview of identified splice site mutations in donor sites (DS) and acceptor sites (AS) of the <i>ATP7A</i> gene. The mutations are located in exon-intron boundaries in either the intervening sequence (IVS) or in the exon sequence (E). The various mutations lead to different MD phenotypes classified as classical MD (C), atypical MD (A), OHS (O) or unknown (−). The mutations were analysed with the online bioinformatics tool, Human Splicing Finder (HSF), to predict the splicing signals in wild-type and mutated DNA sequences. The strength of the splice sites is indicated by the consensus value (CV) and the CV variation (ΔCV). Potential cryptic splice sites predicted with HSF are given. Effects on pre-mRNA splicing that have been identified <i>in vivo</i> are listed.</p>*<p>Found in this study.</p

CV and ΔCV in relation to MD patient phenotypes.

<p>Using HSF, each mutation is analysed for the effect on the given splice site based on the two parameters CV and ΔCV. Mutated splice sites with CVs above 70 are likely to retain some activity. Conversely, splice sites with CVs below 70 are considered inactive. ΔCV-reductions of less than 10% (or * less than 7% at position +4) are likely to retain some wild-type splice site activity, whereas ΔCV-reductions of more than 10% (7% at position +4) are considered broken and inactive <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0018599#pone.0018599-Desmet1" target="_blank">[10]</a>. The mutations are categorized based on the CV- and ΔCV-values obtained in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0018599#pone-0018599-t001" target="_blank">Table 1</a> “Mild MD” covers atypical MD and OHS phenotypes. Patients with unknown clinical phenotype are not included.</p