SLC35A2-CDG: Functional characterization, expanded molecular, clinical, and biochemical phenotypes of 30 unreported Individuals.
UDP-galactose
congenital disorders of glycosylation
glycoside
nucleotide sugar transporter
Journal
Human mutation
ISSN: 1098-1004
Titre abrégé: Hum Mutat
Pays: United States
ID NLM: 9215429
Informations de publication
Date de publication:
07 2019
07 2019
Historique:
received:
30
10
2018
revised:
11
02
2019
accepted:
20
02
2019
pubmed:
1
3
2019
medline:
18
3
2020
entrez:
1
3
2019
Statut:
ppublish
Résumé
Pathogenic de novo variants in the X-linked gene SLC35A2 encoding the major Golgi-localized UDP-galactose transporter required for proper protein and lipid glycosylation cause a rare type of congenital disorder of glycosylation known as SLC35A2-congenital disorders of glycosylation (CDG; formerly CDG-IIm). To date, 29 unique de novo variants from 32 unrelated individuals have been described in the literature. The majority of affected individuals are primarily characterized by varying degrees of neurological impairments with or without skeletal abnormalities. Surprisingly, most affected individuals do not show abnormalities in serum transferrin N-glycosylation, a common biomarker for most types of CDG. Here we present data characterizing 30 individuals and add 26 new variants, the single largest study involving SLC35A2-CDG. The great majority of these individuals had normal transferrin glycosylation. In addition, expanding the molecular and clinical spectrum of this rare disorder, we developed a robust and reliable biochemical assay to assess SLC35A2-dependent UDP-galactose transport activity in primary fibroblasts. Finally, we show that transport activity is directly correlated to the ratio of wild-type to mutant alleles in fibroblasts from affected individuals.
Identifiants
pubmed: 30817854
doi: 10.1002/humu.23731
pmc: PMC6661012
mid: NIHMS1015203
doi:
Substances chimiques
Monosaccharide Transport Proteins
0
UDP-galactose translocator
0
Uridine Diphosphate Galactose
2956-16-3
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
908-925Subventions
Organisme : NICHD NIH HHS
ID : U54 HD090257
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM008638
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK099551
Pays : United States
Organisme : NHGRI NIH HHS
ID : U01 HG007703
Pays : United States
Informations de copyright
© 2019 Wiley Periodicals, Inc.
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