SLC10A7 mutations cause a skeletal dysplasia with amelogenesis imperfecta mediated by GAG biosynthesis defects - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Nature Communications Année : 2018

SLC10A7 mutations cause a skeletal dysplasia with amelogenesis imperfecta mediated by GAG biosynthesis defects

Jeanne Amiel
  • Fonction : Auteur
  • PersonId : 853872
Arnaud Bruneel
  • Fonction : Auteur
  • PersonId : 944740

Résumé

Skeletal dysplasia with multiple dislocations are severe disorders characterized by dislocations of large joints and short stature. The majority of them have been linked to pathogenic variants in genes encoding glycosyltransferases, sulfotransferases or epimerases required for glycosaminoglycan synthesis. Using exome sequencing, we identify homozygous mutations in SLC10A7 in six individuals with skeletal dysplasia with multiple dislocations and amelogenesis imperfecta. SLC10A7 encodes a 10-transmembrane-domain transporter located at the plasma membrane. Functional studies in vitro demonstrate that SLC10A7 mutations reduce SLC10A7 protein expression. We generate a Slc10a7−/− mouse model, which displays shortened long bones, growth plate disorganization and tooth enamel anomalies, recapitulating the human phenotype. Furthermore, we identify decreased heparan sulfate levels in Slc10a7−/− mouse cartilage and patient fibroblasts. Finally, we find an abnormal N-glycoprotein electrophoretic profile in patient blood samples. Together, our findings support the involvement of SLC10A7 in glycosaminoglycan synthesis and specifically in skeletal development.
Fichier principal
Vignette du fichier
s41467-018-05191-8.pdf (5.24 Mo) Télécharger le fichier
Origine : Publication financée par une institution
Loading...

Dates et versions

hal-01914333 , version 1 (06-11-2018)

Identifiants

Citer

Johanne Dubail, Céline Huber, Sandrine Chantepie, Stephan Sonntag, Beyhan Tuysuz, et al.. SLC10A7 mutations cause a skeletal dysplasia with amelogenesis imperfecta mediated by GAG biosynthesis defects. Nature Communications, 2018, 9 (1), pp.3087. ⟨10.1038/s41467-018-05191-8⟩. ⟨hal-01914333⟩
658 Consultations
89 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More