Journal
AMERICAN JOURNAL OF HUMAN GENETICS
Volume 89, Issue 3, Pages 407-414Publisher
CELL PRESS
DOI: 10.1016/j.ajhg.2011.08.008
Keywords
-
Categories
Funding
- Iranian National Science Foundation
- Max Planck Innovation Fund
- German Federal Ministry of Education and Research [MRNET 01GS08161-2]
- German Research Foundation [GE 801/10-1]
Ask authors/readers for more resources
The genetic variants leading to impairment of intellectual performance are highly diverse and are still poorly understood. ST3GAL3 encodes the Golgi enzyme beta-galactoside-alpha 2,3-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
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available