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.