Mucopolysaccharidosis IV (MPS IV): Most Common MPS Type
MPS IV was discovered to be the most common type in the current Iranian cohort accounting for 34.9% of the patients, even though MPS IV has never been reported as the most common type in previous studies. Geographical origin of MPS IV patients along with the distribution pattern of 3 frequent variants in GALNS gene are depicted in Figure 4. c.860C>T was the most common variant in theGALNS gene discovered in 6.6% (6/90) of MPS IV patients. This variant has been classified as one of the top 10 most common variants in the GALNS gene with reports from the Polish, American Caucasian, Austrian, Macedonian, Turkish, Greek, and Indian population (Bidchol et al. 2014; Morrone et al. 2014). The distribution of this variant among the Iranian population was rather scattered across the country, but 4 of the 6 patients harboring this variant were from the southern and southwestern provinces.
The second most common variant among MPS IV patients was c.319G>A with a 4.4% (4/90) frequency, which has been previously reported in Italy, China, and Dubai (Al-Jasmi et al. 2013; Tomatsu et al. 2004; Wang et al. 2010). All the patients diagnosed with this variant were from the East Azerbaijan province in the northwest of Iran, with parents from the same city, Tabriz. Moreover, the paternal side of MPS-235 and MPS-142 were both from a small village near Tabriz, suggesting that a founder effect may have resulted in distribution of c.319G>A in East Azerbaijan. Since c.319G>A is responsible for 50% of MPS IV patients in East Azerbaijan (4/8), a stepwise genetic testing considering the prevalence of this variant can be developed, suggesting genetic analysis of c.319G>A for MPS IV patients originated from this region before performing a more comprehensive analysis.
The c.1042A>G variant, reported for the first time in this study, was found in 3 patients and was the third most common variant in MPS IV patients. Notably, two of these patients were from the same city in the northeastern province of Khorasan-Razavi, and the other patient was from the northern province of Mazandaran.