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Your search keyword '"Apolipoprotein C-III glycosylation"' showing total 2 results
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2 results on '"Apolipoprotein C-III glycosylation"'

1. Novel congenital disorder of O-linked glycosylation caused by GALNT2 loss of function.

Author

Zilmer, Monica, Edmondson, Andrew C, Khetarpal, Sumeet A, Alesi, Viola, Zaki, Maha S, Rostasy, Kevin, Madsen, Camilla G, Lepri, Francesca R, Sinibaldi, Lorenzo, Cusmai, Raffaella, Novelli, Antonio, Issa, Mahmoud Y, Fenger, Christina D, Jamra, Rami Abou, Reutter, Heiko, Briuglia, Silvana, Agolini, Emanuele, Hansen, Lars, Petäjä-Repo, Ulla E, and Hintze, John

Subjects
*RESEARCH, *ANIMAL experimentation, *GLYCOSYLATION, *RESEARCH methodology, *DEVELOPMENTAL disabilities, *EVALUATION research, *MEDICAL cooperation, *RATS, *COMPARATIVE studies, *APOLIPOPROTEINS, *TRANSFERASES, *RESEARCH funding, *GENETIC techniques, *MICE, *GENEALOGY
Abstract

Congenital disorders of glycosylation are a growing group of rare genetic disorders caused by deficient protein and lipid glycosylation. Here, we report the clinical, biochemical, and molecular features of seven patients from four families with GALNT2-congenital disorder of glycosylation (GALNT2-CDG), an O-linked glycosylation disorder. GALNT2 encodes the Golgi-localized polypeptide N-acetyl-d-galactosamine-transferase 2 isoenzyme. GALNT2 is widely expressed in most cell types and directs initiation of mucin-type protein O-glycosylation. All patients showed loss of O-glycosylation of apolipoprotein C-III, a non-redundant substrate for GALNT2. Patients with GALNT2-CDG generally exhibit a syndrome characterized by global developmental delay, intellectual disability with language deficit, autistic features, behavioural abnormalities, epilepsy, chronic insomnia, white matter changes on brain MRI, dysmorphic features, decreased stature, and decreased high density lipoprotein cholesterol levels. Rodent (mouse and rat) models of GALNT2-CDG recapitulated much of the human phenotype, including poor growth and neurodevelopmental abnormalities. In behavioural studies, GALNT2-CDG mice demonstrated cerebellar motor deficits, decreased sociability, and impaired sensory integration and processing. The multisystem nature of phenotypes in patients and rodent models of GALNT2-CDG suggest that there are multiple non-redundant protein substrates of GALNT2 in various tissues, including brain, which are critical to normal growth and development. [ABSTRACT FROM AUTHOR]

Published
2020
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2. Novel congenital disorder of O-linked glycosylation caused by GALNT2 loss of function

Author

Elena Gardella, Damir Musaev, Cecilia Vitali, Emanuele Agolini, Sumeet A. Khetarpal, Kimiyo Raymond, Daniel J. Rader, Camilla Gøbel Madsen, Valentina Stanley, Antonio Novelli, Andrew C. Edmondson, W. Timothy O'Brien, Heiko Reutter, John Hintze, Kristen Liedtke, Mahmoud Y. Issa, Lars Hansen, Christina Fenger, Kevin Rostasy, Rami Abou Jamra, Maha S. Zaki, Francesca Romana Lepri, Ulla E. Petäjä-Repo, Joseph G. Gleeson, Rikke S. Møller, Silvana Briuglia, Katrine T. Schjoldager, Lorenzo Sinibaldi, Viola Alesi, Guido Rubboli, Raffaella Cusmai, and Monica Zilmer

Subjects
0301 basic medicine, Male, medicine.medical_specialty, Glycosylation, Adolescent, Congenital disorders of glycosylation, O-glycosylation, GALNT2, Apolipoprotein C-III glycosylation, HDL-cholesterol, Developmental Disabilities, Biology, 03 medical and health sciences, chemistry.chemical_compound, Mice, Young Adult, 0302 clinical medicine, Loss of Function Mutation, Internal medicine, medicine, Animals, Humans, Congenital disorders of glycosylation, Global developmental delay, Child, O-glycosylation, Apolipoprotein C-III, Original Articles, medicine.disease, HDL-cholesterol, Pedigree, Rats, Developmental disorder, 030104 developmental biology, Endocrinology, chemistry, GALNT2, Child, Preschool, O-linked glycosylation, Apolipoprotein C-III glycosylation, N-Acetylgalactosaminyltransferases, Apolipoprotein C3, lipids (amino acids, peptides, and proteins), Female, Neurology (clinical), Congenital disorder of glycosylation, Lipid glycosylation, 030217 neurology & neurosurgery, Congenital disorder
Abstract

Congenital disorders of glycosylation are a growing group of rare genetic disorders caused by deficient protein and lipid glycosylation. Here, we report the clinical, biochemical, and molecular features of seven patients from four families with GALNT2-congenital disorder of glycosylation (GALNT2-CDG), an O-linked glycosylation disorder. GALNT2 encodes the Golgi-localized polypeptide N-acetyl-d-galactosamine-transferase 2 isoenzyme. GALNT2 is widely expressed in most cell types and directs initiation of mucin-type protein O-glycosylation. All patients showed loss of O-glycosylation of apolipoprotein C-III, a non-redundant substrate for GALNT2. Patients with GALNT2-CDG generally exhibit a syndrome characterized by global developmental delay, intellectual disability with language deficit, autistic features, behavioural abnormalities, epilepsy, chronic insomnia, white matter changes on brain MRI, dysmorphic features, decreased stature, and decreased high density lipoprotein cholesterol levels. Rodent (mouse and rat) models of GALNT2-CDG recapitulated much of the human phenotype, including poor growth and neurodevelopmental abnormalities. In behavioural studies, GALNT2-CDG mice demonstrated cerebellar motor deficits, decreased sociability, and impaired sensory integration and processing. The multisystem nature of phenotypes in patients and rodent models of GALNT2-CDG suggest that there are multiple non-redundant protein substrates of GALNT2 in various tissues, including brain, which are critical to normal growth and development.

Published
2020
Full Text
View/download PDF

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