Discussion

This study is the largest cohort of Iranian MPS population with precise tracking of ethnicity and geographical origin which unveils patterns of the distribution of frequent mutations in the MPS patients as well as redirecting MPS to their appropriate treatment options. Here, we discuss the logistics behind the algorithm used to optimize the re-diagnosis process and the inevitable limitations. In this study, the genetic profiling of 289 clinically diagnosed MPS patients confirmed MPS diagnosis in 258 (89.3%), and identified 5 (1.7%) with non-MPS inborn errors of metabolism.
In total, we discovered novel causal variants in 90 patients (34.9%), which is a significant proportion of our cohort, and could be due to the fact our study is the first extensive MPS study of the Iranian population. Although there have been a few studies published in recent years that have contributed to our understanding of the molecular causes of MPS in Iran, the patient pool in those studies was considerably smaller than that of ours. Overall, 18 studies have reported molecular characterization of Iranian MPS patients, comprising 46 MPS I patients, 34 MPS VI patients, 19 MPS III patients, 4 MPS II patients, 4 MPS IV patients, and 1 MPS VII patient (Abbasi et al. 2017; Alaei et al. 2020; Aminzadeh, Malekpour, and Ghandil 2019; Jafaryazdi et al. 2018, 2019; Kamranjam and Alaei 2019; Khorrami et al. 2019; Malekpour, Vakili, and Hamzehloie 2018; Mansour, Rasoul, and B 2007; Martins et al. 2019; Mosallanejad et al. 2020; Nouri et al. 2012; Salehi 2004; Seyedhassani et al. 2015; Shafaat et al. 2020; Taghikhani et al. 2019; Marlies J. Valstar et al. 2010; Yassaee et al. 2017).
Multiethnic nature of the Iranian population has regionalized a number of MPS variants. Additionally, c.962C>T in ARSB(c.962C>T), which was the dominant MPS VI variant in the northwestern provinces of Iran, has also been reported in the neighboring country, Turkey. Detailed documentation of geographic origins, pedigrees, and clinical findings have allowed us to uncover these patterns, which will be discussed in detail in order of prevalence.