Comprehensive validation of a diagnostic strategy for sequencing genes with one or multiple pseudogenes, using pseudoxanthoma elasticum as a model

We propose a diagnostic strategy for the molecular diagnosis of genes with one or more known pseudogene(s) with next-generation sequencing (NGS), using pseudoxanthoma elasticum and ABCC6 as an example. Indeed, the use of NGS for analysis of such genes can be complicated by false positive and negative results. We show in this paper that in contrast to whole exome sequencing, a combined approach of PCR-based targeted enrichment with an adapted mapping algorithm circumvents aspecificities due to pseudogenes in a reliable way.