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, Abou Jamra, R, 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, vol. 143, no. 4, pp. 1114-1126.
https://doi.org/10.1093/brain/awaa063APA
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., Abou Jamra, R., 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/awaa063CBE
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, Abou Jamra R, 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. 143(4):1114-1126.
https://doi.org/10.1093/brain/awaa063MLA
Vancouver
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 ; Abou Jamra, Rami ; 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. In:
Brain. 2020 ; Vol. 143, No. 4. pp. 1114-1126.
Bibtex
@article{22d7306f15334929a2eb60200809e7bd,
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 {Abou Jamra}, Rami 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'Brien, {W Timothy} and Elena Gardella and Guido Rubboli and Rader, {Daniel J} and Schjoldager, {Katrine T} and M{\o}ller, {Rikke S}",
note = "{\textcopyright} The Author(s) (2020). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please email: journals.permissions@oup.com.",
year = "2020",
month = apr,
day = "1",
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 - Abou Jamra, Rami
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
N1 - © The Author(s) (2020). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please email: journals.permissions@oup.com.
PY - 2020/4/1
Y1 - 2020/4/1
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
UR - http://www.scopus.com/inward/record.url?scp=85084423074&partnerID=8YFLogxK
U2 - 10.1093/brain/awaa063
DO - 10.1093/brain/awaa063
M3 - Journal article
C2 - 32293671
VL - 143
SP - 1114
EP - 1126
JO - Brain
JF - Brain
SN - 0006-8950
IS - 4
ER -
