MGAT2 – MGAT2-congenital disorder of glycosylation

MGAT2-congenital disorder of glycosylation is an autosomal recessive multisystemic disease with severe neurological involvement, including global developmental delay. Two unrelated patients harbored biallelic missense variants in the catalytic domain of UDP-GlcNAc:α-6-D-mannoside β-1,2-N-acetylglucosaminyltransferase II: c.869C>T (p.Ser290Phe) and c.785A>G (p.His262Arg) (PMID:8808595). Segregation analysis in 23 relatives revealed 13 heterozygous carriers with 33–68% reduction in GnT-II activity, confirming autosomal recessive inheritance (PMID:8808595). In vitro expression in a baculovirus/insect cell system demonstrated near-complete loss of enzyme activity and protein stability, consistent with a loss-of-function mechanism. Mgat2-null mice exhibit deficient GnT-II activity, complex N-glycan loss, early postnatal lethality, and multisystemic defects mirroring human CDG-IIa (PMID:11805078; PMID:12417412).

References

• American journal of human genetics • 1996 • Mutations in the MGAT2 gene controlling complex N-glycan synthesis cause carbohydrate-deficient glycoprotein syndrome type II, an autosomal recessive disease with defective brain development. PMID:8808595
• Glycobiology • 2001 • Modeling human congenital disorder of glycosylation type IIa in the mouse: conservation of asparagine-linked glycan-dependent functions in mammalian physiology and insights into disease pathogenesis. PMID:11805078
• Biochimica et biophysica acta • 2002 • Mice with a homozygous deletion of the Mgat2 gene encoding UDP-N-acetylglucosamine:alpha-6-D-mannoside beta1,2-N-acetylglucosaminyltransferase II: a model for congenital disorder of glycosylation type IIa. PMID:12417412

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