Congenital Disorder of Glycosylation Type Ik (CDG-Ik): A Defect of Mannosyltransferase I

Kranz, Christian; Denecke, Jonas; Lehle, Ludwig; Sohlbach, Kristina; Jeske, Stefanie; Meinhardt, Friedhelm; Rossi, Rainer; Gudowius, Sonja; Marquardt, Thorsten

doi:10.1086/382493

Cited by 77 publications

(50 citation statements)

References 18 publications

(14 reference statements)

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“…This indicates that TMEM165 deficiency affects the glycosylation of various proteins and that the changes are not restricted to transferrin. The faint pattern of the second sample can be explained by the patient's nephrotic syndrome since it has been observed that the consequent protein loss can account for faint patterns in IEF (Kranz et al 2004).…”

Section: Discussionmentioning

confidence: 99%

TMEM165 Deficiency: Postnatal Changes in Glycosylation

et al. 2015

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Congenital disorders of glycosylation form a rapidly growing group of inherited metabolic diseases. As glycosylation affects proteins all over the organism, a mutation in a single gene leads to a multisystemic disorder. We describe a patient with TMEM165-CDG with facial dysmorphism, nephrotic syndrome, cardiac defects, enlarged cerebral ventricles, feeding problems, and neurological involvement. Having confirmed the diagnosis via prenatal diagnostics, we were able to observe the glycosylation right from birth, finding a pathological pattern already on the first day of life. Within the next few weeks, hypoglycosylation progressed to less sialylated and then also to hypogalactosylated isoforms. On the whole, there has not been much published evidence concerning postnatal glycosylation and its adaptational process. This is the first paper reporting changes in glycosylation patterns over the first postnatal weeks in TMEM165-CDG.

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Section: Discussionmentioning

confidence: 99%

TMEM165 Deficiency: Postnatal Changes in Glycosylation

et al. 2015

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“…Compared with other CDG types, the phenotype in ALG1-CDG is very severe, with rapid development of microcephaly, seizures refractory to treatment, progressive stupor, and death in early infancy (Kranz et al 2004). The hypoglycosylation of liver-derived serum glycoproteins is more profound than in other types of CDG-I.…”

Section: Discussionmentioning

confidence: 96%

Two Argentinean Siblings with CDG-Ix: A Novel Type of Congenital Disorder of Glycosylation?

et al. 2011

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Congenital disorders of glycosylation (CDG) are genetic diseases caused by abnormal protein and lipid glycosylation. In this chapter, we report the clinical, biochemical, and molecular findings in two siblings with an unidentified CDG (CDG-Ix). They are the first and the third child of healthy consanguineous Argentinean parents. Patient 1 is now a 11-year-old girl, and patient 2 died at the age of 4 months. Their clinical picture involved liver dysfunction in the neonatal period, psychomotor retardation, microcephaly, seizures, axial hypotonia, feeding difficulties, and hepatomegaly. Patient 1 also developed strabismus and cataract. They showed a type 1 pattern of serum sialotransferrin. Enzymatic analysis for phosphomannomutase and phosphomannose isomerase in leukocytes and fibroblasts excluded PMM2-CDG and MPI-CDG. Lipid-linked oligosaccharide (LLO) analysis showed a normal profile. Therefore, this result could point to a deficiency in the dolichol metabolism. In this context, ALG8-CDG, DPAGT1-CDG, and SRD5A3-CDG were analyzed and no defects were identified. In conclusion, we could not identify the genetic deficiency in these patients yet. Further studies are underway to identify the basic defect in them, taking into account the new CDG types that have been recently described.

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“…We previously identified the HMT-1 gene, orthologous to the yeast ALG1 (31), which encodes human MT-I (32). Since then, it has been demonstrated by several groups that dysfunction of HMT-1 results in CDG-Ik (33)(34)(35)(36). Of seven substitutional mutations reported to drastically decrease MT-I activity, S150R and G145D mutations are notable, because Ser 150 and Gly 145 residues of human MT-I are neither conserved nor located within a conserved domain.…”

Section: E-6 Perspectivesmentioning

confidence: 99%

Physical Interactions among Human Glycosyltransferases Involved in Dolichol-Linked Oligosaccharide Biosynthesis

Takahashi¹,

Gao²

2012

TIGG

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In eukaryotic glycoproteins, the N-glycan plays an important role with respect to both their structure and function. On the rough endoplasmic reticulum (rER) membrane, the N-glycan precursor is biosynthesized as a dolichol-linked oligosaccharide (DLO), which consists of fourteen sugars linked to pyrophosphoryl-dolichol. For completion of fulllength DLO (Glc 3 Man 9 GlcNAc 2 -PP-dolichol), activities of at least eleven glycosyltransferases localized on the rER membrane are essential. Although twelve human genes for these enzymes have been identified, any physical interactions among them have not yet been systematically analyzed. In this review, we describe several physical interactions among them that were uncovered using the yeast split-ubiquitin system. Moreover, on the basis of observations obtained by this technique, novel models for networking among human glycosyltransferases can be proposed.

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Congenital Disorder of Glycosylation Type Ik (CDG-Ik): A Defect of Mannosyltransferase I

Cited by 77 publications

References 18 publications

TMEM165 Deficiency: Postnatal Changes in Glycosylation

TMEM165 Deficiency: Postnatal Changes in Glycosylation

Two Argentinean Siblings with CDG-Ix: A Novel Type of Congenital Disorder of Glycosylation?

Physical Interactions among Human Glycosyltransferases Involved in Dolichol-Linked Oligosaccharide Biosynthesis

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