title: 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.affiliation: Monique and Jacques Roboh Department of Genetic Research, the Department of Genetic and Metabolic Diseases, Hadassah, Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Simon
authors.initials: S
authors.lastname: Edvardson
authors.forename: Anna-Maria
authors.initials: AM
authors.lastname: Baumann
authors.forename: Martina
authors.initials: M
authors.lastname: Mühlenhoff
authors.forename: Oliver
authors.initials: O
authors.lastname: Stephan
authors.forename: Andreas W
authors.initials: AW
authors.lastname: Kuss
authors.forename: Avraham
authors.initials: A
authors.lastname: Shaag
authors.forename: Liqun
authors.initials: L
authors.lastname: He
authors.forename: Shamir
authors.initials: S
authors.lastname: Zenvirt
authors.forename: Raimo
authors.initials: R
authors.lastname: Tanzi
authors.forename: Rita
authors.initials: R
authors.lastname: Gerardy-Schahn
authors.forename: Orly
authors.initials: O
authors.lastname: Elpeleg
mesh_terms: D000293:Adolescent; D017668:Age of Onset; D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use; D016466:CHO Cells; D002648:Child; D002675:Child, Preschool; D006224:Cricetinae; D003412:Cricetulus; D004252:DNA Mutational Analysis; D004569:Electroencephalography; D004827:Epilepsy / Q000188:drug therapy / Q000209:etiology; D000939:Epitopes / Q000235:genetics; D005091:Exons / Q000235:genetics; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D007223:Infant; D008607:Intellectual Disability / Q000453:epidemiology; D065768:Lennox Gastaut Syndrome; D008297:Male; D010375:Pedigree; D012799:Sialyltransferases / Q000172:deficiency*; D013036:Spasms, Infantile / Q000453:epidemiology / Q000235:genetics*; D005680:gamma-Aminobutyric Acid / Q000502:physiology; D000094663:beta-Galactoside alpha-2,3-Sialyltransferase
chemical_list: D000927:Anticonvulsants; D000939:Epitopes; D005680:gamma-Aminobutyric Acid; D012799:Sialyltransferases; D000094663:beta-Galactoside alpha-2,3-Sialyltransferase