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

Dubail, J., Huber, C., Chantepie, S., Sonntag, S., Tuysuz, B., Mihci, E., Gordon, C. T., Steichen-Gersdorf, E., Amiel, J., Nur, B., Stolte-Dijkstra, I., van Eerde, A. M., van Gassen, K. L., Breugem, C. C., Stegmann, A., Lekszas, C., Maroofian, R., Karimiani, E. G., Bruneel, A., Seta, N., Munnich, A., Papy-Garcia, D., De La Dure-Molla, M. & Cormier-Daire, V., 6-Aug-2018, In : Nature Communications. 9, 15 p., 3087.

Research output: Contribution to journalArticleAcademicpeer-review

  • Johanne Dubail
  • Celine Huber
  • Sandrine Chantepie
  • Stephan Sonntag
  • Beyhan Tuysuz
  • Ercan Mihci
  • Christopher T. Gordon
  • Elisabeth Steichen-Gersdorf
  • Jeanne Amiel
  • Banu Nur
  • Irene Stolte-Dijkstra
  • Albertien M. van Eerde
  • Koen L. van Gassen
  • Corstiaan C. Breugem
  • Alexander Stegmann
  • Caroline Lekszas
  • Reza Maroofian
  • Ehsan Ghayoor Karimiani
  • Arnaud Bruneel
  • Nathalie Seta
  • Arnold Munnich
  • Dulce Papy-Garcia
  • Muriel De La Dure-Molla
  • Valerie Cormier-Daire

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.

Original languageEnglish
Article number3087
Number of pages15
JournalNature Communications
Publication statusPublished - 6-Aug-2018



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