CSGALNACT1-congenital disorder of glycosylation: A mild skeletal dysplasia with advanced bone age.

Détails

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Etat: Public
Version: Final published version
Licence: CC BY-NC-ND 4.0
ID Serval
serval:BIB_CED95552EEA3
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
CSGALNACT1-congenital disorder of glycosylation: A mild skeletal dysplasia with advanced bone age.
Périodique
Human mutation
Auteur(s)
Mizumoto S., Janecke A.R., Sadeghpour A., Povysil G., McDonald M.T., Unger S., Greber-Platzer S., Deak K.L., Katsanis N., Superti-Furga A., Sugahara K., Davis E.E., Yamada S., Vodopiutz J.
ISSN
1098-1004 (Electronic)
ISSN-L
1059-7794
Statut éditorial
Publié
Date de publication
03/2020
Peer-reviewed
Oui
Volume
41
Numéro
3
Pages
655-667
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Résumé
Congenital disorders of glycosylation (CDGs) comprise a large number of inherited metabolic defects that affect the biosynthesis and attachment of glycans. CDGs manifest as a broad spectrum of disease, most often including neurodevelopmental and skeletal abnormalities and skin laxity. Two patients with biallelic CSGALNACT1 variants and a mild skeletal dysplasia have been described previously. We investigated two unrelated patients presenting with short stature with advanced bone age, facial dysmorphism, and mild language delay, in whom trio-exome sequencing identified novel biallelic CSGALNACT1 variants: compound heterozygosity for c.1294G>T (p.Asp432Tyr) and the deletion of exon 4 that includes the start codon in one patient, and homozygosity for c.791A>G (p.Asn264Ser) in the other patient. CSGALNACT1 encodes CSGalNAcT-1, a key enzyme in the biosynthesis of sulfated glycosaminoglycans chondroitin and dermatan sulfate. Biochemical studies demonstrated significantly reduced CSGalNAcT-1 activity of the novel missense variants, as reported previously for the p.Pro384Arg variant. Altered levels of chondroitin, dermatan, and heparan sulfate moieties were observed in patients' fibroblasts compared to controls. Our data indicate that biallelic loss-of-function mutations in CSGALNACT1 disturb glycosaminoglycan synthesis and cause a mild skeletal dysplasia with advanced bone age, CSGALNACT1-CDG.
Mots-clé
CSGALNACT1-CDG, CSGalNAcT-1, advanced bone age, cartilage and brain development, glycosaminoglycan, joint laxity, macrocephaly, proteoglycan, short stature
Pubmed
Web of science
Open Access
Oui
Création de la notice
14/11/2019 12:01
Dernière modification de la notice
15/01/2021 8:11
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