Genetic Causes of Mental Retardation in Golestan Province

Objective: About 70 percent of mental retardation can be attributed to genetic causes. Whereas the recognization of genetic causes of mental retardation causes better programming and more precision council for prevention and control of mental retardation, so the aim of this study is to investigate the genetic causes of mental retardation in Golestan province. Materials & Methods: In this descriptive research which is a cross-sectional and applied study, fifty families with two or more affected children from different parts of Golestan province were collected with cooperation of Golestan state welfare organization and by simple sampling method. Mental retardation of affected people had been previously proved by physicians. Blood samples of patients and controls in the family were prepared. Patients were investigated for dysmorphism and microcephaly. Cytogenetic study, metabolic test, fragile X test, and linkage analysis for seven gene loci known for autosomal recessive primary microcephaly (MCPH) was carried out. Results: Chromosomal abnormalities were not observed in any family. One out of fifty families revealed fragile X syndrome and ten were affected to MCPH. Five out of ten microcephaly families were linked to MCPH (autosomal recessive primary microcephaly) loci. Conclusion: Autosomal recessive primary microcephaly (MCPH)make up about 20% 0f all mental retardation in Golestan province. This prevalence is very remarkable

ST3GAL3 Mutations Impair the Development of Higher Cognitive Functions

The genetic variants leading to impairment of intellectual performance are highly diverse and are still poorly understood. ST3GAL3 encodes the Golgi enzyme β-galactoside-α2,3-sialyltransferase-III that in humans predominantly forms the sialyl Lewis a epitope on proteins. ST3GAL3 resides on chromosome 1 within the MRT4 locus previously identified to associate with nonsyndromic autosomal recessive intellectual disability. We searched for the disease-causing mutations in the MRT4 family and a second independent consanguineous Iranian family by using a combination of chromosome sorting and next-generation sequencing. Two different missense changes in ST3GAL3 cosegregate with the disease but were absent in more than 1000 control chromosomes. In cellular and biochemical test systems, these mutations were shown to cause ER retention of the Golgi enzyme and drastically impair ST3Gal-III functionality. Our data provide conclusive evidence that glycotopes formed by ST3Gal-III are prerequisite for attaining and/or maintaining higher cognitive functions