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.