Loss of NDST1 N -sulfotransferase activity is associated with autosomal recessive intellectual disability - Aix-Marseille Université Accéder directement au contenu
Article Dans Une Revue Human Molecular Genetics Année : 2023

Loss of NDST1 N -sulfotransferase activity is associated with autosomal recessive intellectual disability

Elham Khosrowabadi
  • Fonction : Auteur
Cécile Mignon-Ravix
  • Fonction : Auteur
Florence Riccardi
  • Fonction : Auteur
Pierre Cacciagli
  • Fonction : Auteur
Béatrice Desnous
Sabine Sigaudy
  • Fonction : Auteur
Mathieu Milh
  • Fonction : Auteur
Lena Kjellén

Résumé

Intellectual Disability (ID) is the major cause of handicap, affecting nearly 3% of the general population, and is highly genetically heterogenous with more than a thousand genes involved. Exome sequencing performed in two independent families identified the same missense variant, p.(Gly611Ser), in the NDST1 (N-deacetylase/N-sulfotransferase member 1) gene. This variant had been previously found in ID patients of two other families but has never been functionally characterized. The NDST1 gene encodes a bifunctional enzyme that catalyzes both N-deacetylation and N-sulfation of N-acetyl-glucosamine residues during heparan sulfate (HS) biosynthesis. This step is essential because it influences the downstream enzymatic modifications and thereby determines the overall structure and sulfation degree of the HS polysaccharide chain. To discriminate between a rare polymorphism and a pathogenic variant, we compared the enzymatic properties of wild-type and mutant NDST1 proteins. We found that the p.(Gly611Ser) variant results in a complete loss of N-sulfotransferase activity while the N-deacetylase activity is retained. NDST1 shows the highest and the most homogeneous expression in the human cerebral structures compared to the other members of the NDST gene family. These results indicate that a loss of NDST1 N-sulfation activity is associated with impaired cognitive functions.
Fichier sous embargo
Fichier sous embargo
0 1 24
Année Mois Jours
Avant la publication
vendredi 21 juin 2024
Fichier sous embargo
vendredi 21 juin 2024
Connectez-vous pour demander l'accès au fichier

Dates et versions

hal-04404827 , version 1 (19-01-2024)

Identifiants

Citer

Elham Khosrowabadi, Cécile Mignon-Ravix, Florence Riccardi, Pierre Cacciagli, Béatrice Desnous, et al.. Loss of NDST1 N -sulfotransferase activity is associated with autosomal recessive intellectual disability. Human Molecular Genetics, 2023, ⟨10.1093/hmg/ddad203⟩. ⟨hal-04404827⟩
8 Consultations
4 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More