Conclusion

In summary, this study presents the genetic profiling of the largest cohort of Iranian MPS patients consisting of 289 unrelated families. Our comprehensive diagnostic approach was able to molecularly characterize 258 patients harboring putatively causal variants in 8 MPS genes, in addition to identification of five non-MPS IEM patients. Notably, 87.2% of the diagnosed patients were homozygous, besides a high proportion of consanguineous marriages among this cohort (83%). MPS IV was the most common type in this study followed by MPS I and MPS VI, contrary to previous reports where MPS VI contributed to a considerably low proportion of the patients. Furthermore, we identified a region-specific pattern for several predominant pathogenic variants (eg. ARSB : c.430G>A, c.962C>T and GALNS : c.319G>A) which provides insight into genetic epidemiology of MPS and can facilitate a more cost-effective, time-efficient diagnostic approach.