A familial case of Paget’s disease of bone with mutation at exon 8 of the sequestosome gene

25 Nov
2011

Introduction

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


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