LETTER TO JMG

Clinical and molecular features of three patients with congenital disorders of glycosylation type Ih (CDG-Ih) (ALG8 deficiency)

E Schollen¹, C G Frank², L Keldermans¹, R Reyntjens¹, C E Grubenmann³, P T Clayton⁴, B G Winchester⁴, J Smeitink⁵, R A Wevers⁶, M Aebi², T Hennet³, G Matthijs¹

¹ Center for Human Genetics, University of Leuven, Leuven, Belgium
² Institute of Microbiology, Swiss Federal Institute of Technology, Zürich, Switzerland
³ Institute of Physiology, University of Zürich, Zürich, Switzerland
⁴ Great Ormond Street Hospital for Children and Institute of Child Health, University College London, London, UK
⁵ Department of Paediatrics, University Medical Center Nijmegen, Nijmegen, The Netherlands
⁶ Laboratory of Paediatrics and Neurology, University Medical Center Nijmegen, Nijmegen, The Netherlands

Correspondence to:
Correspondence to:
G Matthijs
Center for Human Genetics, University of Leuven, Herestraat 49, B-3000 Leuven, Belgium; Gert.Matthijs@uz.kuleuven.ac.be

Received 4 December 2003

Accepted 6 February 2004

Abbreviations: CDG, congenital disorders of glycosylation; CPY, carboxypeptidase Y; CST, castanospermine; ER, endoplasmic reticulum; LLO, lipid-linked oligosaccharide; MPI, phosphomannose isomerase; NLO, N-linked oligosaccharide; NMD, nonsense-mediated mRNA decay

Keywords: ALG8; CDG-Ih; congenital disorders of glycosylation; mutations; N-glycosylation

The first 150 words of the full text of this article appear below.

Protein glycosylation is an essential post-translational modification of various proteins, affecting their folding, sorting, and function. Inborn defects in the assembly and processing of glycans on glycoproteins are known as congenital disorders of glycosylation (CDG) and can affect both N- and O-glycosylation (for reviews see Marquardt and Denecke,¹ Jaeken,² and Grunewald et al³). N-glycosylation defects and especially defects in the assembly of the dolichol linked N-glycan precursor in the endoplasmic reticulum (ER) (CDG-I) result in hypoglycosylation of many kinds of (serum) glycoproteins. CDG-I is therefore a group of multisystemic disorders.

The assembly of the N-glycan precursor in the ER is a highly ordered process involving at least 30 known gene products. Mutations in 11 of these (PMM2, MPI, ALG6, DPM1, ALG3, MPDU1, ALG12, ALG8, ALG2, DPAGT1, and ALG1) have been shown to cause CDG type I (CDG-Ia to CDG-Ik).^2,4–10 Although it remains difficult to define a characteristic clinical phenotype . . . [Full text of this article]

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Cohn, R. D., Eklund, E., Bergner, A. L., Casella, J. F., Woods, S. L., Althaus, J., Blakemore, K. J., Fox, H. E., Hoover-Fong, J. E., Hamosh, A., Braverman, N. E., Freeze, H. H., Boyadjiev, S. A. (2006). Intracranial Hemorrhage as the Initial Manifestation of a Congenital Disorder of Glycosylation. Pediatrics 118: e514-e521 [Abstract] [Full Text]  
• Kelleher, D. J., Gilmore, R. (2006). An evolving view of the eukaryotic oligosaccharyltransferase. Glycobiology 16: 47R-62R [Abstract] [Full Text]  
• Kralovicova, J., Christensen, M. B., Vorechovsky, I. (2005). Biased exon/intron distribution of cryptic and de novo 3' splice sites. Nucleic Acids Res 33: 4882-4898 [Abstract] [Full Text]