摘要：Congenital disorders of glycosylation (CDG) constitute an ever-growing group of genetic diseases affecting the glycosylation of proteins. CDG individuals usually present with severe multisystem disorders. MAN1B1-CDG is a CDG with nonspecific clinical symptoms such as intellectual deficiency and developmental delay. Although up to 40 affected individuals were described so far, its final diagnosis is not straightforward using common biochemical methods due to the trace-level accumulation of defective glycan structures. In this study, we present three unreported MAN1B1-CDG individuals and propose a decision tree to reach diagnosis using a panel of techniques ranging from exome sequencing to gel electrophoresis and mass spectrometry. The occurrence of MAN1B1-CDG in patients showing unexplained intellectual disability and development delay, as well as a particular transferrin glycosylation profile, can be ascertained notably using matrix assisted laser desorption/ionization – time of flight (MALDI-TOF) mass spectrometry analysis of endo -β-acetylglucosaminidase H-released serum N-glycans. In addition to reporting new pathogenic variants and additional clinical signs such as hypersialorrhea, we highlight particular biochemical features of MAN1B1-CDG with potential glycoprotein-specific glycosylation defects.
关键词：CDG ; Hypersialorrhea ; Intellectual disability ; MAN1B1 ; N-glycan mass spectrometry ; 2-DE two-dimensional electrophoresis ; A1AT α1-antitrypsin ; ApoC-III apolipoprotein C-III ; BMI body mass index ; CDG congenital disorder(s) of glycosylation ; CE capillary electrophoresis ; DD developmental delay ; DWI Diffusion-weighted imaging ; Endo H endo -ß- N -acetylglucosaminidase H ; ER endoplasmic reticulum ; ESI-QTOF electrospray ionization ;quadrupole time of flight ; FLAIR fluid-attenuated inversion recovery ; HPLC high performance liquid chromatography ; Hpt haptoglobin ; ID intellectual disability ; M6 Man 6 GlcNAc 2 ; M8A/B/C Man 8 GlcNAc 2 lacking the first/middle/third terminal mannose ; M9 Man 9 GlcNAc 2 ; MALDI-TOF matrix assisted laser desorption/ionization ;time of flight ; Man mannose ; MRI magnetic resonance imaging ; MS mass spectrometry ; PNGase F peptide-N-glycosidase F ; Trf transferrin ; WES whole exome sequencing
