Copy Number Variation (CNV) analysis
Patients with no positive findings in SNV analysis or those who had monoallelic variants were further analyzed for CNV events using the Ion Reporter CNV caller tool. Depth of coverage data were retrieved from BAM files and normalized against a reference set of 100 normal controls. CNVs overlapping MPS genes were individually reviewed and prioritized if: they had deletion status; passed quality metrics set by the software; and were not shared by several patients. Identified CNVs were validated using multiplex PCRs targeting exons overlapping CNVs as well as non-deleted exons flanking the CNV.