Pedigree Analysis
In total, autosomal recessive MPS types (I, III, IV, VI) encompassed
93% of genetically confirmed cases in IMPRESsion study, which could be
explained by the observed consanguinity rate of 81.2% in the studied
families. Identifying the variant in these families allows them to seek
prenatal diagnosis or other preventive measures after comprehensive
genetic counseling.
A universal study carried out by Morrone et al. (2014) on the
alterations in the GALNS gene listing 277 unique variants in this
gene, discovered that 48% of the MPS IV patients were homozygous, while
39% harbored two different variants in the GALNS gene, hence
deemed as compound heterozygous. On the contrary, 94.4% (85/90) of the
MPS IV patients in the IMPRESsion study were homozygous. This staggering
difference is likely to be the result of high prevalence of
consanguinity in the Iranian population. To further illustrate, only 8
MPS IV patients had non-consanguineous parents, resulting in 91.1%
(82/90) consanguinity among MPS IV patients. Similarly, 54.8% of MPS VI
patients in Tomanin et al.’s (2018) comprehensive study were homozygous
for the ARSB gene variants, while our cohort consisted of 96.6%
(56/58) homozygous MPS VI patients with a 84.4% (49/58) rate of
consanguinity, in which the only compound heterozygous MPS VI patient
had non-consanguineous parents. Overall, the high prevalence of
consanguinity in the Iranian population led to higher frequencies of
homozygous patients compared to the western populations.