Paget’s disease of bone (PDB) is a disorder of bone metabolism reported to affect up to 3% of Caucasian over 55 years of age. PDB is a genetically heterogeneous disorder characterized by abnormal osteoclastic activity leading to bone destruction and macroscopic deformities, which cause bone pain and pathological fractures. There is evidence of genetic abnormalities in its pathogenesis, and at least 8 different human chromosomal loci have been correlated to PDB. The PDB 3 locus in chromosome 5q35-qter hosts the SQ STM1/p62 gene, whose mutations account for most of the sporadic and familial forms of PDB reported in the literature. SQSTM1/p62 gene encodes the SQSTM1/p62 protein, that is component of the NF-kB signaling pathway crucial for osteoclastic differentiation and activation. The exon 8 DNA sequence accounts for the ubiquitin protein-binding domain (UBA) and represents a mutational hot spot area. An abnormal UBA region is reported to account the inability to bind to ubiquitin with consequential accumulation of sesquestosome protein. Different mutations of SQSTM1/p62 have been reported in French Canadian PDB families, and a recent observation seems to confirm the causal relationship between this gene and Paget’s disease of bone also in sporadic Italian patients.
We report a case of a family whose members are affected by polyostotic PDB with mutation at exon 8 of SQSTM1/p62 gene. Don’t blow your budget on pharmacy items cialis 200mg now