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

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

Hamartomatous Angiolipoma of the Parotid Gland (Sialoangiolipoma)

Mesenchymal tumors of the salivary glands are rare and mostly localized to the parotid gland. We report on the clinico-pathological features of a distinct parotid tumor occurred in a newborn, showing glandular structures admixed with mature lipocytes and blood vessels in variable proportions. This was a well-circumscribed and slowly growing nodule of the superficial parotid lobe, mostly reddish in color with white-yellowish striations. Microscopically, a distinct lobular architecture was evident, along with normal-appearing acinar and ductal structures with interposed loose fibrous stroma. The latter contained aggregates of mature lipocytes and variably sized blood vessels. The morphological features of the lesion reported herein recapitulate those of sialolipoma but also include the presence of a prominent vascular component intimately admixed with both the glandular and the adipose tissues. At variance with salivary lipoadenoma, the glandular component in the current case distinctly showed all the cellular components of normal salivary (serous) glands. In consideration of the young age of the patient, the minimal growth rate and the histological features of the lesion, we hypothesize a hamartomatous origin for this lesion and propose the designation of sialoangiolipoma