We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Multi-allelic origin of congenital disorder of glycosylation (CDG)-Ic.
- Authors
Imbach, Timo; Grünewald, Stephanie; Schenk, Barbara; Burda, Patricie; Schollen, Els; Wevers, Ron A.; Jaeken, Jaak; de Klerk, Johannis B.C.; Berger, Eric G.; Matthijs, Gert; Aebi, Markus; Hennet, Thierry
- Abstract
Congenital disorders of glycosylation (CDG), formerly known as carbohydrate-deficient glycoprotein syndrome, represent a family of genetic diseases with variable clinical presentations. Common to all types of CDG characterized to date is a defective Asn-linked glycosylation caused by enzymatic defects of N-glycan synthesis. Previously, we have identified a mutation in the ALG6 α1,3 glucosyltransferase gene as the cause of CDG-Ic in four related patients. Here, we present the identification of seven additional cases of CDG-Ic among a group of 35 untyped CDG patients. Analysis of lipid-linked oligosaccharides in fibroblasts confirmed the accumulation of dolichyl pyrophosphate-Man9GlcNAc2 in the CDG-Ic patients. The genomic organization of the human ALG6 gene was determined, revealing 14 exons spread over 55 kb. By polymerase chain reaction amplification and sequencing of ALG6 exons, three mutations, in addition to the previously described A333 V substitution, were detected in CDG-Ic patients. The detrimental effect of these mutations on ALG6 activity was confirmed by complementation of alg6 yeast mutants. Haplotype analysis of CDG-Ic patients revealed a founder effect for the ALG6 allele bearing the A333 V mutation. Although more than 80% of CDG are type Ia, CDG-Ic may be the second most common form of the disease.
- Subjects
GENETIC disorders; GLYCOSYLATION; GENETIC mutation; GLYCOSYLTRANSFERASES; GLYCOPROTEINS; HUMAN genetics
- Publication
Human Genetics, 2000, Vol 106, Issue 5, p538
- ISSN
0340-6717
- Publication type
Article
- DOI
10.1007/s004390050022