Genetic aspects of the Paget’s disease of bone: concerns on the introduction of DNA-based tests in the clinical practice. Advantages and disadvantages of its application
Article first published online: 9 JUN 2010
© 2010 The Authors. Journal Compilation © 2010 Stichting European Society for Clinical Investigation Journal Foundation
European Journal of Clinical Investigation
Volume 40, Issue 7, pages 655–667, July 2010
How to Cite
Alberto, F., Francesca, M., Laura, M., Antonietta, A. and Luisa, B. M. (2010), Genetic aspects of the Paget’s disease of bone: concerns on the introduction of DNA-based tests in the clinical practice. Advantages and disadvantages of its application. European Journal of Clinical Investigation, 40: 655–667. doi: 10.1111/j.1365-2362.2010.02312.x
- Issue published online: 9 JUN 2010
- Article first published online: 9 JUN 2010
- Received 12 February 2010; accepted 13 April 2010
Vol. 40, Issue 10, 963, Article first published online: 13 SEP 2010
- DNA-based test;
- genetics of Paget’s disease of bone;
- metabolic bone disorder;
- Paget’s disease of bone;
Eur J Clin Invest 2010; 40 (7): 655–667
Background A large amount of genetic studies have clearly demonstrated the existence of a genetic susceptibility to Paget’s disease of bone (PDB). Although the disease is genetically heterogeneous, the SQSTM1/p62 gene, encoding a protein with a pathophysiological role in both osteoclast differentiation and activity, has been found worldwide to harbour germline mutations in most of the PDB patients from geographically distant populations originating from different areas of Europe, both in sporadic and familial cases.
Materials and Methods Thus, SQSTM1/p62 gene mutations may confer an increased lifetime risk of developing PDB.
Results Several different genotype-phenotype analyses have shown a high penetrance for such mutations. These results suggest the opportunity to perform genetic testing in affected individuals and then, after the identification of a SQSTM1/p62 gene germline mutation, in their relatives as a real and concrete strategy to increase the diagnostic sensitivity in most of the asymptomatic mutant carriers. However, it is of note to underlie that an incomplete penetrance for SQSTM1/p62 gene mutations has also been reported.
Conclusions In light of all these contradictory evidences, a review on whether, when and why apply the DNA test to those subjects, its interpretation and clinical application is necessary. In fact, a growing number of preventive care options are now available to affected patients and families and the process of systematically assessing risk is becoming increasingly important for both patients and physicians.