Copyright © 2004 The American Society of Human Genetics. All rights reserved.
The American Journal of Human Genetics, Volume 74, Issue 3, 545-551, 1 March 2004
doi:10.1086/382493
Congenital Disorder of Glycosylation Type Ik (CDG-Ik): A Defect of Mannosyltransferase I
Christian Kranz1, Jonas Denecke1, Ludwig Lehle3, Kristina Sohlbach1, Stefanie Jeske2, Friedhelm Meinhardt2, Rainer Rossi4, Sonja Gudowius5 and Thorsten Marquardt1, 
, 
1 Klinik und Poliklinik für Kinderheilkunde, Münster, Germany
2 Institut für Molekulare Mikrobiologie und Biotechnologie, Münster, Germany
3 Lehrstuhl für Zellbiologie und Pflanzenphysiologie, Regensburg, Germany
4 Klinikum Neukölln, Kinderklinik, Berlin
5 Universitätskinderklinik, Düsseldorf, Germany
Address for correspondence and reprints: Dr. Thorsten Marquardt, Klinik und Poliklinik für Kinderheilkunde, Albert-Schweitzer-Straße 33, 48149 Münster, GermanyAbstract
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.
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