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- Title
<italic>ZNF687</italic> mutations are frequently found in pagetic patients from South Italy: implication in the pathogenesis of Paget's disease of bone.
- Authors
Divisato, G.; Scotto di Carlo, F.; Petrillo, N.; Esposito, T.; Gianfrancesco, F.
- Abstract
Paget's disease of bone (PDB) is a skeletal disorder whose molecular basis is not fully elucidated. However, 10% of patients show a familial PDB and 35% of them carry mutations in the <italic>SQSTM1</italic> gene. We recently reported a founder mutation (p.Pro937Arg) in the <italic>ZNF687</italic> gene, underlying PDB complicated by giant cell tumor (GCT/PDB) and rarely occurring in PDB patients without neoplastic degeneration. Since 80% of Italian GCT/PDB patients derive from Avellino, we hypothesized that <italic>ZNF687</italic> mutation rate was higher in this region than elsewhere. Interestingly, our molecular analysis on 30 PDB patients showed that 33% hosted <italic>ZNF687</italic> mutations, with the p.Pro937Arg identified in 8 familial cases. Two novel <italic>ZNF687</italic> mutations (p.Pro665Leu and p.Gln784Glu) were detected in 2 sporadic patients. Only 2 subjects were positive for the p.Pro392Leu mutation in <italic>SQSTM1. ZNF687</italic>‐mutated patients showed a severe PDB, with a remarkable number of affected sites. in vitro studies revealed that the <italic>ZNF687</italic>‐mutant osteoclasts appeared as giant sized with up to 150 nuclei, never described in PDB. Finally, we also confirmed the causality of the p.Pro937Arg mutation in 4 additional GCT/PDB cases deriving from the same geographic area, indicating that PDB and GCT/PDB represent 2 sides of the same coin.
- Subjects
OSTEOCLASTS; OSTEITIS deformans; OSTEOCLASTOGENESIS; GIANT cell tumors; ODONTOCLASTS
- Publication
Clinical Genetics, 2018, Vol 93, Issue 6, p1240
- ISSN
0009-9163
- Publication type
Article
- DOI
10.1111/cge.13247