Fabry disease: Detection of Alu-mediated exon duplication by NGS

Monogenetic diseases can be analyzed routinely by targeted DNA sequencing. If causative variants are not found, complementary methods like RNA sequencing or analysis of copy number variations by multiplex ligation-dependent probe amplification have to be considered. In the latter, especially exonic duplications or deletions can be detected, but the precise sites of mutations remain unclear. As we demonstrate in this casuistic report of Fabry disease, next-generation sequencing (NGS) of a long-range PCR product can identify the recombination site directly and illuminate the underlying molecular mechanism.