TY  - JOUR
A1  - Dubail, Johanne
A1  - Huber, Céline
A1  - Chantepie, Sandrine
A1  - Sonntag, Stephan
A1  - Tüysüz, Beyhan
A1  - Mihci, Ercan
A1  - Gordon, Christopher T.
A1  - Steichen-Gersdorf, Elisabeth
A1  - Amiel, Jeanne
A1  - Nur, Banu
A1  - Stolte-Dijkstra, Irene
A1  - van Eerde, Albertien M.
A1  - van Gassen, Koen L.
A1  - Breugem, Corstiaan C.
A1  - Stegmann, Alexander
A1  - Lekszas, Caroline
A1  - Maroofian, Reza
A1  - Karimiani, Ehsan Ghayoor
A1  - Bruneel, Arnaud
A1  - Seta, Nathalie
A1  - Munnich, Arnold
A1  - Papy-Garcia, Dulce
A1  - De La Dure-Molla, Muriel
A1  - Cormier-Daire, Valérie
T1  - SLC10A7 mutations cause a skeletal dysplasia with amelogenesis imperfecta mediated by GAG biosynthesis defects
JF  - Nature Communications
N2  - 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.
KW  - bone development
KW  - disease genetics
KW  - medical genetics
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-226377
VL  - 9
ER  -