West syndrome caused by ST3Gal-III deficiency.

Abstract

West syndrome consists of infantile spasms, hypsarrhythmia, and developmental arrest. Most patients remain mentally retarded and many develop Lennox-Gastaut syndrome. Using homozygosity mapping followed by exome sequencing we identified an ST3GAL3 mutation in three infants with West syndrome. ST3GAL3 encodes a sialyltransferase involved in the biosynthesis of sialyl-Lewis epitopes on cell surface-expressed glycoproteins. The mutation affected an essential sialyl-motif and abolished enzymatic activity. Abnormalities in proteins involved in forebrain γ-aminobutyric acid (GABA)ergic synaptic growth and function were recently proposed to account for infantile spasms. Dysfunctional ST3GAL3 may thus result in perturbation of the posttranslational sialylation of proteins in these pathways.

• Authors: Simon Edvardson, Anna-Maria Baumann, Martina Mühlenhoff, Oliver Stephan, Andreas W Kuss, Avraham Shaag, Liqun He, Shamir Zenvirt, Raimo Tanzi, Rita Gerardy-Schahn, Orly Elpeleg
• Journal: Epilepsia (Epilepsia) Vol. 54 Issue 2 Pg. e24-7 (Feb 2013) ISSN: 1528-1167 [Electronic] United States
• PMID: 23252400 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Wiley Periodicals, Inc. © 2012 International League Against Epilepsy.

Chemical References

• Anticonvulsants
• Epitopes
• gamma-Aminobutyric Acid
• Sialyltransferases
• beta-Galactoside alpha-2,3-Sialyltransferase

Topics

• Adolescent
• Age of Onset
• Animals
• Anticonvulsants (therapeutic use)
• CHO Cells
• Child
• Child, Preschool
• Cricetinae
• Cricetulus
• DNA Mutational Analysis
• Electroencephalography
• Epilepsy (drug therapy, etiology)
• Epitopes (genetics)
• Exons (genetics)
• Female
• Genetic Linkage
• Humans
• Infant
• Intellectual Disability (epidemiology)
• Lennox Gastaut Syndrome
• Male
• Pedigree
• Sialyltransferases (deficiency)
• Spasms, Infantile (epidemiology, genetics)
• gamma-Aminobutyric Acid (physiology)
• beta-Galactoside alpha-2,3-Sialyltransferase