Ann Lab Med.  2025 Jan;45(1):112-115. 10.3343/alm.2024.0226.

The First Korean Case of MAN1B1-Congenital Disorder of Glycosylation Diagnosed Using Whole-Exome Sequencing and Matrix-Assisted Laser Desorption Ionization Time-of-Flight Mass Spectrometry

• Kim KB
• Lee GS
• Shin S
• Kim DC
• Seo D
• Kweon H
• Kang H
• Park S
• Kim DH
• Ryoo N
• Lee S
• Ha JS

• KMID: 2563865
• DOI: http://doi.org/10.3343/alm.2024.0226

Figure

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  Fig. 1 Distribution of MAN1B1 variants reported in the literatures and this paper. (A) Genomic locations of variants associated with MAN1B1-congenital disorder of glycosylation. The black rectangles indicate the 13 exons, and the gray rectangles indicate the 5′-untranslated region and the 12 introns. The upward-pointing text indicates single-nucleotide substitutions, and the downward-facing text indicates frameshifting deletions, except for one large deletion variant (c.465+1460_620+527del). The two variants found in our patient are highlighted in bold red. (B) Alignment of the mutations to the functional domains of endoplasmic reticulum mannosyl-oligosaccharide 1,2-alpha-mannosidase (NP_057303.2) encoded by MAN1B1 (NM_016219.5). The left vertical bar represents the number of times the mutation has been reported, and the horizontal bar below indicates the location of amino acids. The corresponding amino acid changes for the two variants reported in this paper are highlighted in bold red.

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  Fig. 2 Mass spectra of N-glycan profiling using Matrix-assisted Laser Desorption Ionization Time-of-flight Mass Spectrometry following peptide-N-glycosidase F treatment. The mass spectra of samples from the patient (A) revealed an increase in mannose-rich glycans (upward black triangle) and a decrease in N-acetyl glucosamine-binding glycans (downward black triangle) compared with that in the healthy control (B). A hybrid-type N-glycan was observed at m/z 1913.7 (red), which is specific to patients with MAN1B1 deficiency. Green circles, mannose; yellow circles, galactose; blue squares, N-acetyl glucosamine; red triangles, fucose; and purple diamonds, sialic acid.

Reference

References

1. Ng BG, Freeze HH. 2018; Perspectives on glycosylation and its congenital disorders. Trends Genet. 34:466–76. DOI: 10.1016/j.tig.2018.03.002. PMID: 29606283. PMCID: PMC5959770.

2. Kasapkara CS, Olgac A, Kilic M, Keldermans L, Matthijs G, Jaeken J. 2021; MAN1B1-CDG: novel patients and novel variant. J Pediatr Endocrinol Metab. 34:1207–9. DOI: 10.1515/jpem-2021-0038. PMID: 34162022.

3. Okamoto N, Ohto T, Enokizono T, Wada Y, Kohmoto T, Imoto I, et al. 2021; Siblings with MAN1B1-CDG showing novel biochemical profiles. Cells. 10:3117. DOI: 10.3390/cells10113117. PMID: 34831340. PMCID: PMC8618856. PMID: d8762ed4b28945f98a16c4990c2bea59.

4. Sakhi S, Cholet S, Wehbi S, Isidor B, Cogne B, Vuillaumier-Barrot S, et al. 2021; MAN1B1-CDG: three new individuals and associated biochemical profiles. Mol Genet Metab Rep. 28:100775. DOI: 10.1016/j.ymgmr.2021.100775. PMID: 34141584. PMCID: PMC8182421.

5. Gustafsson OJ, Briggs MT, Condina MR, Winderbaum LJ, Pelzing M, McColl SR, et al. 2015; MALDI imaging mass spectrometry of N-linked glycans on formalin-fixed paraffin-embedded murine kidney. Anal Bioanal Chem. 407:2127–39. DOI: 10.1007/s00216-014-8293-7. PMID: 25434632. PMCID: PMC4357650.

6. Gupta S, Fahiminiya S, Wang T, Dempsey Nunez L, Rosenblatt DS, Gibson WT. 2016; Somatic overgrowth associated with homozygous mutations in both MAN1B1 and SEC23A. Cold Spring Harb Mol Case Stud. 2:a000737. DOI: 10.1101/mcs.a000737. PMID: 27148587. PMCID: PMC4853519.

7. Sun AH, Collette JR, Sifers RN. 2020; The cytoplasmic tail of human mannosidase Man1b1 contributes to catalysis-independent quality control of misfolded alpha1-antitrypsin. Proc Natl Acad Sci U S A. 117:24825–36. DOI: 10.1073/pnas.1919013117. PMID: 32958677. PMCID: PMC7547240.

8. Rafiq MA, Kuss AW, Puettmann L, Noor A, Ramiah A, Ali G, et al. 2011; Mutations in the alpha 1,2-mannosidase gene, MAN1B1, cause autosomal-recessive intellectual disability. Am J Hum Genet. 89:176–82. DOI: 10.1016/j.ajhg.2011.06.006. PMID: 21763484. PMCID: PMC3135808.

9. Hoffjan S, Epplen JT, Reis A, Abou Jamra R. 2015; MAN1B1 mutation leads to a recognizable phenotype: a case report and future prospects. Mol Syndromol. 6:58–62. DOI: 10.1159/000371399. PMID: 26279649. PMCID: PMC4521065.

10. Balasubramanian M, Johnson DS. DDD Study. 2019; MAN1B-CDG: Novel variants with a distinct phenotype and review of literature. Eur J Med Genet. 62:109–14. DOI: 10.1016/j.ejmg.2018.06.011. PMID: 29908352.