Skeletal dysplasias are a large group of disorders characterized by specific anomalies in bone development and associated with features including dislocations of large joints, scoliosis, short stature and a varying combination of organ malformations. The majority of them are caused by variants in genes that encode glycosyltransferases, sulfotransferases, epimerases or transporters. These enzymes are essential for the biosynthesis of glycosaminoglycanes, important components of the extracellular matrix. By means of exome sequencing, an international collaboration of researchers have now identified homozygous mutations in the SLC10A7 gene in six patients with a specific type of skeletal dysplasia associated with multiple dislocations and amelogenesis imperfecta. The gene product of SLC10A7 is a 10-transmembrane domain transporter located at the plasma membrane, the substrate of which is not yet known. The researchers performed various functional studies including a mouse model with the identified mutation which recapitulates several features of the human phenotype including shortened long bones, disorganization of the growth plate and tooth enamel anomalies. Their analyses showed that SLC10A7 plays a role in glycosaminoglycane biosynthesis and specifically in skeletal and teeth development.

The results of this study have been published in Nature Communications.

Dubail J, Huber C, Chantepie S, […] Cormier-Daire V. SLC10A7 mutations cause a skeletal dysplasia with amelogenesis imperfecta mediated by GAG biosynthesis defects. Nat Commun. 2018 Aug 6;9(1):3087. doi: 10.1038/s41467-018-05191-8.