MAN1B1 Deficiency: An Unexpected CDG-II

English version České info

Congenital disorders of glycosylation (CDG) are a group of rare metabolic diseases, due to impaired protein and lipid glycosylation. In the present study, exome sequencing was used to identify MAN1B1 as the culprit gene in an unsolved CDG-II patient. Subsequently, 6 additional cases with MAN1B1-CDG were found. All individuals presented slight facial dysmorphism, psychomotor retardation and truncal obesity. Generally, MAN1B1 is believed to be an ER resident alpha-1,2-mannosidase acting as a key factor in glycoprotein quality control by targeting misfolded proteins for ER-associated degradation (ERAD). However, recent studies indicated a Golgi localization of the endogenous MAN1B1, suggesting a more complex role for MAN1B1 in quality control. We were able to confirm that MAN1B1 is indeed localized to the Golgi complex instead of the ER. Furthermore, we observed an altered Golgi morphology in all patients' cells, with marked dilatation and fragmentation. We hypothesize that part of the phenotype is associated to this Golgi disruption. In conclusion, we linked mutations in MAN1B1 to a Golgi glycosylation disorder. Additionally, our results support the recent findings on MAN1B1 localization. However, more work is needed to pinpoint the exact function of MAN1B1 in glycoprotein quality control, and to understand the pathophysiology of its deficiency.

Vyšlo v časopise: MAN1B1 Deficiency: An Unexpected CDG-II. PLoS Genet 9(12): e32767. doi:10.1371/journal.pgen.1003989
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1003989

Souhrn

Zdroje

1. JaekenJ, MatthijsG (2007) Congenital disorders of glycosylation: a rapidly expanding disease family. Annual review of genomics and human genetics 8: 261–278 Available: http://www.ncbi.nlm.nih.gov/pubmed/17506657. Accessed 2 February 2013.

2. TheodoreM, MoravaE (2011) Congenital disorders of glycosylation: sweet news. Current opinion in pediatrics 23: 581–587 Available: http://www.ncbi.nlm.nih.gov/pubmed/21970833. Accessed 7 February 2013.

3. MatthijsG, RymenD, MillónMBB, SoucheE, RaceV (2013) Approaches to homozygosity mapping and exome sequencing for the identification of novel types of CDG. Glycoconjugate journal 30: 67–76 Available: http://www.ncbi.nlm.nih.gov/pubmed/22983704. Accessed 7 February 2013.

4. StevensFJ, ArgonY (1999) Protein folding in the ER. Seminars in cell & developmental biology 10: 443–454 Available: http://www.ncbi.nlm.nih.gov/pubmed/10597627. Accessed 7 February 2013.

5. JakobCA, BurdaP, RothJ, AebiM (1998) Degradation of misfolded endoplasmic reticulum glycoproteins in Saccharomyces cerevisiae is determined by a specific oligosaccharide structure. The Journal of cell biology 142: 1223–1233 Available: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2149342&tool=pmcentrez&rendertype=abstract. Accessed 7 February 2013.

6. BurkeJ, LipariF, IgdouraS, HerscovicsA (1996) The Saccharomyces cerevisiae processing alpha 1,2-mannosidase is localized in the endoplasmic reticulum, independently of known retrieval motifs. European journal of cell biology 70: 298–305 Available: http://www.ncbi.nlm.nih.gov/pubmed/8864657. Accessed 7 February 2013.

7. GonzalezDS, KaravegK, Vandersall-NairnAS, LalA, MoremenKW (1999) Identification, expression, and characterization of a cDNA encoding human endoplasmic reticulum mannosidase I, the enzyme that catalyzes the first mannose trimming step in mammalian Asn-linked oligosaccharide biosynthesis. The Journal of biological chemistry 274: 21375–21386 Available: http://www.ncbi.nlm.nih.gov/pubmed/10409699. Accessed 7 February 2013.

8. PanS, WangS, UtamaB, HuangL, BlokN, et al. (2011) Golgi localization of ERManI defines spatial separation of the mammalian glycoprotein quality control system. Molecular biology of the cell 22: 2810–2822 Available: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3154878&tool=pmcentrez&rendertype=abstract. Accessed 7 February 2013.

9. RafiqMA, KussAW, PuettmannL, NoorA, RamiahA, et al. (2011) Mutations in the alpha 1,2-mannosidase gene, MAN1B1, cause autosomal-recessive intellectual disability. American journal of human genetics 89: 176–182 Available: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3135808&tool=pmcentrez&rendertype=abstract. Accessed 7 February 2013.

10. NajmabadiH, HuH, GarshasbiM, ZemojtelT, AbediniSS, et al. (2011) Deep sequencing reveals 50 novel genes for recessive cognitive disorders. Nature 478: 57–63 Available: http://www.ncbi.nlm.nih.gov/pubmed/21937992. Accessed 5 February 2013.

11. LederkremerGZ (2009) Glycoprotein folding, quality control and ER-associated degradation. Current opinion in structural biology 19: 515–523 Available: http://www.ncbi.nlm.nih.gov/pubmed/19616933. Accessed 7 February 2013.

12. CamirandA, HeysenA, GrondinB, HerscovicsA (1991) Glycoprotein biosynthesis in Saccharomyces cerevisiae. Isolation and characterization of the gene encoding a specific processing alpha-mannosidase. The Journal of biological chemistry 266: 15120–15127 Available: http://www.ncbi.nlm.nih.gov/pubmed/1714453. Accessed 7 February 2013.

13. De PraeterCM, GerwigGJ, BauseE, NuytinckLK, VliegenthartJF, et al. (2000) A novel disorder caused by defective biosynthesis of N-linked oligosaccharides due to glucosidase I deficiency. American journal of human genetics 66: 1744–1756 Available: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1378052&tool=pmcentrez&rendertype=abstract. Accessed 7 February 2013.

14. EsmonB, EsmonPC, SchekmanR (1984) Early steps in processing of yeast glycoproteins. The Journal of biological chemistry 259: 10322–10327 Available: http://www.ncbi.nlm.nih.gov/pubmed/6381483. Accessed 8 February 2013.

15. TremblayLO, HerscovicsA (1999) Cloning and expression of a specific human alpha 1,2-mannosidase that trims Man9GlcNAc2 to Man8GlcNAc2 isomer B during N-glycan biosynthesis. Glycobiology 9: 1073–1078 Available: http://www.ncbi.nlm.nih.gov/pubmed/10521544. Accessed 7 February 2013.

16. CabralCM, LiuY, SifersRN (2001) Dissecting glycoprotein quality control in the secretory pathway. Trends in Biochemical Sciences 26: 619–624 Available: http://dx.doi.org/10.1016/S0968-0004(01)01942-9. Accessed 15 July 2013.

17. WuX, SteetRA, BohorovO, BakkerJ, NewellJ, et al. (2004) Mutation of the COG complex subunit gene COG7 causes a lethal congenital disorder. Nature medicine 10: 518–523 Available: http://www.ncbi.nlm.nih.gov/pubmed/15107842. Accessed 15 July 2013.

18. RymenD, KeldermansL, RaceV, RégalL, DeconinckN, et al. (2012) COG5-CDG: expanding the clinical spectrum. Orphanet journal of rare diseases 7: 94 Available: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3697985&tool=pmcentrez&rendertype=abstract. Accessed 11 June 2013.

19. KornakU, ReyndersE, DimopoulouA, van ReeuwijkJ, FischerB, et al. (2008) Impaired glycosylation and cutis laxa caused by mutations in the vesicular H+-ATPase subunit ATP6V0A2. Nature genetics 40: 32–34 Available: http://www.ncbi.nlm.nih.gov/pubmed/18157129. Accessed 15 July 2013.

20. CarchonHA, ChevignéR, FalmagneJ-B, JaekenJ (2004) Diagnosis of congenital disorders of glycosylation by capillary zone electrophoresis of serum transferrin. Clinical chemistry 50: 101–111 Available: http://www.ncbi.nlm.nih.gov/pubmed/14633925. Accessed 29 January 2013.

21. MillsPB, MillsK, MianN, WinchesterBG, ClaytonPT (2003) Mass spectrometric analysis of glycans in elucidating the pathogenesis of CDG type IIx. Journal of inherited metabolic disease 26: 119–134 Available: http://www.ncbi.nlm.nih.gov/pubmed/12889655. Accessed 8 February 2013.

22. FaidV, ChiratF, SetaN, FoulquierF, MorelleW (2007) A rapid mass spectrometric strategy for the characterization of N- and O-glycan chains in the diagnosis of defects in glycan biosynthesis. Proteomics 7: 1800–1813 Available: http://www.ncbi.nlm.nih.gov/pubmed/17520685. Accessed 8 February 2013.

23. LivakKJ, SchmittgenTD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods (San Diego, Calif) 25: 402–408 Available: http://www.ncbi.nlm.nih.gov/pubmed/11846609. Accessed 28 January 2013.

24. FoulquierF, Harduin-LepersA, DuvetS, MarchalI, MirAM, et al. (2002) The unfolded protein response in a dolichyl phosphate mannose-deficient Chinese hamster ovary cell line points out the key role of a demannosylation step in the quality-control mechanism of N-glycoproteins. The Biochemical journal 362: 491–498 Available: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1222411&tool=pmcentrez&rendertype=abstract. Accessed 8 February 2013.