Kranz, Christian et al., Congenital Disorder of Glycosylation Type Ik (CDG-Ik): A Defect of Mannosyltransferase I, American journal of human genetics , 74(3), 2004, pp. 545-551
This study describes the discovery of a new inherited disorder of glycosylation named .CDG-Ik.. CDG-Ik (congenital disorder of glycoslyation type Ik) is based on a defect of human mannosyltransferase I (MT-I [MIM 605907]), an enzyme necessary for the elongation of dolichol-linked chitobiose during N-glycan biosynthesis. Mutations in semiconserved regions in the corresponding gene, HMT-1 (yeast homologue, Alg1), in two patients caused drastically reduced enzyme activity, leading to a severe disease with death in early infancy. One patient had a homozygous point mutation (c.773C.T, S258L), whereas the other patient was compound heterozygous for the mutations c.773C.T and c.1025A.C (E342P). Glycosylation and growth of Alg1-deficient PRY56 yeast cells, showing a temperature-sensitive phenotype, could be restored by the human wild-type allele, whereas only slight restoration was observed after transformation with the patients' alleles.