Document Detail


ST3GAL3 mutations impair the development of higher cognitive functions.
MedLine Citation:
PMID:  21907012     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Hao Hu; Katinka Eggers; Wei Chen; Masoud Garshasbi; M Mahdi Motazacker; Klaus Wrogemann; Kimia Kahrizi; Andreas Tzschach; Masoumeh Hosseini; Ideh Bahman; Tim Hucho; Martina Mühlenhoff; Rita Gerardy-Schahn; Hossein Najmabadi; H Hilger Ropers; Andreas W Kuss
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  American journal of human genetics     Volume:  89     ISSN:  1537-6605     ISO Abbreviation:  Am. J. Hum. Genet.     Publication Date:  2011 Sep 
Date Detail:
Created Date:  2011-09-12     Completed Date:  2011-11-22     Revised Date:  2013-06-27    
Medline Journal Info:
Nlm Unique ID:  0370475     Medline TA:  Am J Hum Genet     Country:  United States    
Other Details:
Languages:  eng     Pagination:  407-14     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.
Affiliation:
Department for Human Molecular Genetics, Max-Planck Institute for Molecular Genetics, Berlin, Germany.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
DNA Mutational Analysis
Endoplasmic Reticulum / metabolism
Female
Genetic Predisposition to Disease / genetics*
Humans
Immunoblotting
Immunohistochemistry
Immunoprecipitation
Intellectual Disability / enzymology*,  genetics
Iran
Male
Mutation, Missense / genetics
Pedigree
Plasmids / genetics
Sialyltransferases / genetics*,  metabolism
Chemical
Reg. No./Substance:
EC 2.4.99.-/Sialyltransferases; EC 2.4.99.4/beta-galactoside alpha-2,3-sialyltransferase
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Translation initiator EIF4G1 mutations in familial Parkinson disease.
Next Document:  The molecular origin and consequences of escape from miRNA regulation by HLA-C alleles.