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

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Standard

Novel congenital disorder of O-linked glycosylation caused by GALNT2 loss of function. / 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.; Hintze, John; Raymond, Kimiyo M.; Liedtke, Kristen; Stanley, Valentina; Musaev, Damir; Gleeson, Joseph G.; Vitali, Cecilia; O’Brien, W. Timothy; Gardella, Elena; Rubboli, Guido; Rader, Daniel J.; Schjoldager, Katrine T.; Møller, Rikke S.

I: Brain, Bind 143, Nr. 4, 2020, s. 1114-1126.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Harvard

Zilmer, M, Edmondson, AC, Khetarpal, SA, Alesi, V, Zaki, MS, Rostasy, K, Madsen, CG, Lepri, FR, Sinibaldi, L, Cusmai, R, Novelli, A, Issa, MY, Fenger, CD, Jamra, RA, Reutter, H, Briuglia, S, Agolini, E, Hansen, L, Petäjä-Repo, UE, Hintze, J, Raymond, KM, Liedtke, K, Stanley, V, Musaev, D, Gleeson, JG, Vitali, C, O’Brien, WT, Gardella, E, Rubboli, G, Rader, DJ, Schjoldager, KT & Møller, RS 2020, 'Novel congenital disorder of O-linked glycosylation caused by GALNT2 loss of function', Brain, bind 143, nr. 4, s. 1114-1126. https://doi.org/10.1093/brain/awaa063

APA

Zilmer, M., Edmondson, A. C., Khetarpal, S. A., Alesi, V., Zaki, M. S., Rostasy, K., Madsen, C. G., Lepri, F. R., Sinibaldi, L., Cusmai, R., Novelli, A., Issa, M. Y., Fenger, C. D., Jamra, R. A., Reutter, H., Briuglia, S., Agolini, E., Hansen, L., Petäjä-Repo, U. E., ... Møller, R. S. (2020). Novel congenital disorder of O-linked glycosylation caused by GALNT2 loss of function. Brain, 143(4), 1114-1126. https://doi.org/10.1093/brain/awaa063

Vancouver

Zilmer M, Edmondson AC, Khetarpal SA, Alesi V, Zaki MS, Rostasy K o.a. Novel congenital disorder of O-linked glycosylation caused by GALNT2 loss of function. Brain. 2020;143(4):1114-1126. https://doi.org/10.1093/brain/awaa063

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. ; Hintze, John ; Raymond, Kimiyo M. ; Liedtke, Kristen ; Stanley, Valentina ; Musaev, Damir ; Gleeson, Joseph G. ; Vitali, Cecilia ; O’Brien, W. Timothy ; Gardella, Elena ; Rubboli, Guido ; Rader, Daniel J. ; Schjoldager, Katrine T. ; Møller, Rikke S. / Novel congenital disorder of O-linked glycosylation caused by GALNT2 loss of function. I: Brain. 2020 ; Bind 143, Nr. 4. s. 1114-1126.

Bibtex

@article{6c3665a9015f4d3fb93e55b32383282b,
title = "Novel congenital disorder of O-linked glycosylation caused by GALNT2 loss of function",
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.",
keywords = "Apolipoprotein C-III glycosylation, Congenital disorders of glycosylation, GALNT2, HDL-cholesterol, O-glycosylation",
author = "Monica Zilmer and Edmondson, {Andrew C.} and Khetarpal, {Sumeet A.} and Viola Alesi and Zaki, {Maha S.} and Kevin Rostasy and Madsen, {Camilla G.} and Lepri, {Francesca R.} and Lorenzo Sinibaldi and Raffaella Cusmai and Antonio Novelli and Issa, {Mahmoud Y.} and Fenger, {Christina D.} and Jamra, {Rami Abou} and Heiko Reutter and Silvana Briuglia and Emanuele Agolini and Lars Hansen and Pet{\"a}j{\"a}-Repo, {Ulla E.} and John Hintze and Raymond, {Kimiyo M.} and Kristen Liedtke and Valentina Stanley and Damir Musaev and Gleeson, {Joseph G.} and Cecilia Vitali and O{\textquoteright}Brien, {W. Timothy} and Elena Gardella and Guido Rubboli and Rader, {Daniel J.} and Schjoldager, {Katrine T.} and M{\o}ller, {Rikke S.}",
year = "2020",
doi = "10.1093/brain/awaa063",
language = "English",
volume = "143",
pages = "1114--1126",
journal = "Brain",
issn = "0006-8950",
publisher = "Oxford University Press",
number = "4",

}

RIS

TY - JOUR

T1 - Novel congenital disorder of O-linked glycosylation caused by GALNT2 loss of function

AU - Zilmer, Monica

AU - Edmondson, Andrew C.

AU - Khetarpal, Sumeet A.

AU - Alesi, Viola

AU - Zaki, Maha S.

AU - Rostasy, Kevin

AU - Madsen, Camilla G.

AU - Lepri, Francesca R.

AU - Sinibaldi, Lorenzo

AU - Cusmai, Raffaella

AU - Novelli, Antonio

AU - Issa, Mahmoud Y.

AU - Fenger, Christina D.

AU - Jamra, Rami Abou

AU - Reutter, Heiko

AU - Briuglia, Silvana

AU - Agolini, Emanuele

AU - Hansen, Lars

AU - Petäjä-Repo, Ulla E.

AU - Hintze, John

AU - Raymond, Kimiyo M.

AU - Liedtke, Kristen

AU - Stanley, Valentina

AU - Musaev, Damir

AU - Gleeson, Joseph G.

AU - Vitali, Cecilia

AU - O’Brien, W. Timothy

AU - Gardella, Elena

AU - Rubboli, Guido

AU - Rader, Daniel J.

AU - Schjoldager, Katrine T.

AU - Møller, Rikke S.

PY - 2020

Y1 - 2020

N2 - 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.

AB - 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.

KW - Apolipoprotein C-III glycosylation

KW - Congenital disorders of glycosylation

KW - GALNT2

KW - HDL-cholesterol

KW - O-glycosylation

U2 - 10.1093/brain/awaa063

DO - 10.1093/brain/awaa063

M3 - Journal article

C2 - 32293671

AN - SCOPUS:85084423074

VL - 143

SP - 1114

EP - 1126

JO - Brain

JF - Brain

SN - 0006-8950

IS - 4

ER -

ID: 243008094