Copy Number Variations
Until recently, CNVs could only be detected through non-high throughput techniques such as Sanger sequencing and MLPA, both of which can analyze a limited region of the genome. But in recent years, discovering CNVs with NGS has been made possible through quantitative readout of high-coverage NGS data (Eisenberger et al. 2013). The value of this technique is shown in cohort studies like ours where performing the old techniques for each patient takes more time and effort. In our study, NGS analysis was able to detect 9 CNVs in the MPS patients (Table 3). The gene with the highest number of CNVs was GALNS , with a 6.7% frequency of CNVs among MPS IVA patients. This is in line with the previous reports on the contribution of CNVs to 2-3% of the reportedGALNS variants (Regier, Oetgen, and Tanpaiboon 1993). Furthermore, a whole IDS gene deletion was detected among the 18 MPS I patients, accounting for 5.5% which is compatible with the previous studies reporting a 9% frequency of CNVs in IDS (Scarpa 1993). We also identified two patients with CNVs in HGSNAT andIDUA , but there is no report in the literature about the proportion of patients with CNVs in these two genes.