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.