Chondroitin Sulfate N-acetylgalactosaminyltransferase-1 (CSGalNAcT-1) Deficiency Results in a Mild Skeletal Dysplasia and Joint Laxity.

Détails

ID Serval
serval:BIB_33E3753767A6
Type
Article: article d'un périodique ou d'un magazine.
Sous-type
Etude de cas (case report): rapporte une observation et la commente brièvement.
Collection
Publications
Institution
Titre
Chondroitin Sulfate N-acetylgalactosaminyltransferase-1 (CSGalNAcT-1) Deficiency Results in a Mild Skeletal Dysplasia and Joint Laxity.
Périodique
Human mutation
Auteur(s)
Vodopiutz J., Mizumoto S., Lausch E., Rossi A., Unger S., Janocha N., Costantini R., Seidl R., Greber-Platzer S., Yamada S., Müller T., Jilma B., Ganger R., Superti-Furga A., Ikegawa S., Sugahara K., Janecke A.R.
ISSN
1098-1004 (Electronic)
ISSN-L
1059-7794
Statut éditorial
Publié
Date de publication
01/2017
Peer-reviewed
Oui
Volume
38
Numéro
1
Pages
34-38
Langue
anglais
Notes
Publication types: Case Reports ; Journal Article
Publication Status: ppublish
Résumé
Mutations in genes encoding enzymes responsible for the biosynthesis and structural diversity of glycosaminoglycans (GAGs) cause a variety of disorders affecting bone and connective tissues, including Desbuquois dysplasia (DD). In an infant with prenatal-onset disproportionate short stature, joint laxity, and radiographic findings typical for DD compound-heterozygosity for a large intragenic deletion, and a p.Pro384Arg missense mutation in CSGALNACT1 was found. CSGALNACT1 encodes chondroitin sulfate N-acetylgalactosaminyltransferase-1 (CSGalNAcT-1, ChGn-1), which initiates chondroitin sulfate (CS) chain biosynthesis on the so-called GAG-protein linker region tetrasaccharide. Biochemical studies revealed a reduced GalNAc-transferase activity of the Arg-384 mutant protein, whereas no differences in proteoglycan synthesis in fibroblasts and the GAG content in the urine were found between patient and controls. This is the first description of bi-allelic loss-of-function mutations in CSGALNACT1 that produce a skeletal dysplasia reminiscent of the skeletal dysplasia of Csgalnact1-/- mice, and adds to the genetic heterogeneity of DD.

Mots-clé
Child, Preschool, DNA Mutational Analysis, Enzyme Activation, Exons, Female, Gene Expression, Heterozygote, Humans, Infant, Joint Instability/diagnosis, Joint Instability/genetics, Musculoskeletal Abnormalities/diagnosis, Musculoskeletal Abnormalities/genetics, Mutation, N-Acetylgalactosaminyltransferases/deficiency, N-Acetylgalactosaminyltransferases/genetics, N-Acetylgalactosaminyltransferases/metabolism, Phenotype, Radiography, Recombinant Fusion Proteins/genetics, Recombinant Fusion Proteins/metabolism, Sequence Deletion, Severity of Illness Index, CSGALNACT1, chondroitin sulfate N-acetylgalactosaminyltransferase-1, glycosaminoglycan, proteoglycan, skeletal dysplasia
Pubmed
Web of science
Création de la notice
09/09/2016 9:22
Dernière modification de la notice
20/08/2019 14:20
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