Najmabadi et al. (2007) and Hu et al. (2011) reported 2 unrelated consanguineous Iranian families with nonsyndromic mild to moderate mental retardation.
In affected members of 2 unrelated consanguineous Iranian families with autosomal recessive nonsyndromic mental retardation, including the one reported by Najmabadi et al. (2007), Hu et al. (2011) used linkage analysis, chromosome sorting, and next-generation sequencing and identified ... In affected members of 2 unrelated consanguineous Iranian families with autosomal recessive nonsyndromic mental retardation, including the one reported by Najmabadi et al. (2007), Hu et al. (2011) used linkage analysis, chromosome sorting, and next-generation sequencing and identified 2 different homozygous mutations in the ST3GAL3 gene (A13D, 606494.0001 and D370Y, 606494.0002, respectively). Neither mutation affected the highly conserved sialyl motifs, but rather affected the N-terminal transmembrane domain and C-terminal catalytic domain, respectively. In vitro functional expression studies showed that the mutant proteins were mislocalized to the endoplasmic reticulum and that 1 (D370Y) had loss of catalytic activity. The findings demonstrated a link between the glycoprotein complex, sialyltransferase activity, and higher cognitive functioning.