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ST3GAL3 mutations impair the development of higher cognitive functions

Item Type:Article
Title:ST3GAL3 mutations impair the development of higher cognitive functions
Creators Name:Hu, H. and Eggers, K. and Chen, W. and Garshasbi, M. and Motazacker, M.M. and Wrogemann, K. and Kahrizi, K. and Tzschach, A. and Hosseini, M. and Bahman, I. and Hucho, T. and Muehlenhoff, M. and Gerardy-Schahn, R. and Najmabadi, H. and Ropers, H.H. and Kuss, A.W.
Abstract:The genetic variants leading to impairment of intellectual performance are highly diverse and are still poorly understood. ST3GAL3 encodes the Golgi enzyme beta-galactoside-alpha2,3-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.
Keywords:DNA Mutational Analysis, Endoplasmic Reticulum, Genetic Predisposition to Disease, Immunoblotting, Immunohistochemistry, Immunoprecipitation, Intellectual Disability, Iran, Missense Mutation, Pedigree, Plasmids, Sialyltransferases
Source:American Journal of Human Genetics
Publisher:Cell Press
Page Range:407-414
Date:9 September 2011
Official Publication:https://doi.org/10.1016/j.ajhg.2011.08.008
PubMed:View item in PubMed

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