UMass Chan Medical School Faculty Publications


Mutations in STT3A and STT3B cause two congenital disorders of glycosylation

UMMS Affiliation

Department of Biochemistry and Molecular Pharmacology

Publication Date


Document Type



Adolescent; Cells, Cultured; Child, Preschool; Congenital Disorders of Glycosylation; Consanguinity; Female; Glycosylation; HeLa Cells; Hexosyltransferases; Homozygote; Humans; Male; Membrane Proteins; Point Mutation; Substrate Specificity; Transferrin


Amino Acids, Peptides, and Proteins | Biochemical Phenomena, Metabolism, and Nutrition | Chemical and Pharmacologic Phenomena | Congenital, Hereditary, and Neonatal Diseases and Abnormalities | Genetic Phenomena | Molecular Biology | Molecular Genetics | Nervous System | Nervous System Diseases | Pathological Conditions, Signs and Symptoms


We describe two unreported types of congenital disorders of glycosylation (CDG) which are caused by mutations in different isoforms of the catalytic subunit of the oligosaccharyltransferase (OST). Each isoform is encoded by a different gene (STT3A or STT3B), resides in a different OST complex and has distinct donor and acceptor substrate specificities with partially overlapping functions in N-glycosylation. The two cases from unrelated consanguineous families both show neurologic abnormalities, hypotonia, intellectual disability, failure to thrive and feeding problems. A homozygous mutation (c.1877T > C) in STT3A causes a p.Val626Ala change and a homozygous intronic mutation (c.1539 + 20G > T) in STT3B causes the other disorder. Both mutations impair glycosylation of a GFP biomarker and are rescued with the corresponding cDNA. Glycosylation of STT3A- and STT3B-specific acceptors is decreased in fibroblasts carrying the corresponding mutated gene and expression of the STT3A (p.Val626Ala) allele in STT3A-deficient HeLa cells does not rescue glycosylation. No additional cases were found in our collection or in reviewing various databases. The STT3A mutation significantly impairs glycosylation of the biomarker transferrin, but the STT3B mutation only slightly affects its glycosylation. Additional cases of STT3B-CDG may be missed by transferrin analysis and will require exome or genome sequencing.


alleles, mutation, failure to thrive, fibroblasts, biological markers, catalytic domain, dna, complementary genes, glycosylation, hela cells, homozygote, introns, intellectual disability, protein isoforms, transferrin, muscle hypotonia, feeding difficulties, congenital disorders of glycosylation, genome sequencing, exome donors

DOI of Published Version



Hum Mol Genet. 2013 Nov 15;22(22):4638-45. doi: 10.1093/hmg/ddt312. Link to article on publisher's site

Related Resources

Link to Article in PubMed

Journal/Book/Conference Title

Human molecular genetics

PubMed ID