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Background  Dendritic Cell-Specific Transmembrane Protein (DC-STAMP) is involved in osteoclastogenesis with a key role in mononucleated osteoclasts fusion. We reported in patients with Paget’s disease of bone (PDB) a rare variant (rs62620995) in the  TM7SF4  gene, encoding for DC-STAMP, which changes a highly conserved amino acid, possibly damaging according to in silico predictions. This study aimed at determining the functional effects of this variant on osteoclast phenotype in PDB.    Methods  Fifty ml of peripheral blood were collected in pagetic patients carrier of this variant ( n  = 4) or not ( n  = 4) and healthy controls ( n  = 4). Monocytes were collected after Ficoll gradient and cultured in a medium containing RANKL (40 ng/ml) and hMCSF (25 ng/ml). At the end of the differentiation period, we assessed the osteoclast morphology and bone resorption abilities. We quantified gene expression of  SQSTM1, DC-STAMP, OS9, CREB3, LAMP1, OC-STAMP , and  NFATC1  genes from cell lysates. Proteins encoded by these genes were investigated by Western Blot. Statistical analyses relied on ANOVA followed by Tukey post-tests.    Results  After 21 days of differentiation, the mean number of nuclei per multinucleated cell was significantly higher in pagetic patients carrier of the variant than in healthy controls. Bone resorption abilities were not modified by the variant. qPCR and Western Blot analyses did not provide any differences, but DC-STAMP expression was higher in patients carrier of the variant than in patients non carrier.    Conclusions  This  TM7SF4  rare variant may have an impact on osteoclast morphology and on DC-STAMP expression during osteoclastogenesis. Further analyses are required to understand the role of this variant during osteoclastogenesis in PDB.    Electronic supplementary material  The online version of this article (10.1186/s12881-017-0495-3) contains supplementary material, which is available to authorized users.

Effect of a rare genetic variant of TM7SF4 gene on osteoclasts of patients with Paget’s disease of bone