Evolution of Paget's disease of bone in adults inheriting SQSTM1 mutations

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dc.contributor.author Cundy, Timothy en
dc.contributor.author Rutland, MD en
dc.contributor.author Naot, Dorit en
dc.contributor.author Bolland, Mark en
dc.date.accessioned 2015-12-03T01:10:43Z en
dc.date.issued 2015-09 en
dc.identifier.citation Clinical endocrinology, 2015, 83 (3), pp. 315 - 319 en
dc.identifier.issn 0300-0664 en
dc.identifier.uri http://hdl.handle.net/2292/27645 en
dc.description.abstract Context The cause of Paget's disease of bone (PDB) is unknown, but genetic factors, particularly SQSTM1 mutations, and environmental factors are important. Objective: To investigate the development of PDB in asymptomatic relatives carrying SQSTM1 mutations to determine whether a secular trend towards a less severe phenotype is evident, and to estimate prospectively the rate at which PDB emerged in this genetically susceptible population. Design: We recruited first-degree relatives of patients with PDB [33 adult offspring (mean age 45) and 1 sibling] with a familial SQSTM1 mutation. We determined the presence of PDB with skeletal scintiscans and confirmatory radiographs. Those negative for PDB on the initial scan were investigated again a mean 5·1 years later. Results: The initial skeletal scintiscan demonstrated PDB in six subjects; 26 of the remaining 28 unaffected subjects had a second scintiscan, with two new cases of monostotic PDB diagnosed in 134 patient-years of follow-up. In the total eight adult offspring diagnosed with PDB, the age of diagnosis was greater, by at least 10 years, than that in the 21 probands with clinically identified PDB (P = 0·005). In adult offspring who were older at the time of skeletal scintigraphy than their affected parents were at the time of clinical diagnosis, the difference was even more marked (P < 0·001). In adult offspring with PDB, the disease was significantly less extensive than in their affected parent, as judged by alkaline phosphatase and disease extent (P < 0·003). Conclusions: These findings suggest a substantial gene-environment interaction: the emergence of PDB in offspring inheriting SQSTM1 mutations is delayed by at least a decade, has a substantially attenuated phenotype and occurs at a low rate between the (mean) ages of 45 and 50 years. The nature of the environmental factor is unknown. en
dc.description.uri http://www.ncbi.nlm.nih.gov/pubmed/25664955 en
dc.format.medium Print-Electronic en
dc.language English en
dc.publisher John Wiley & Sons en
dc.relation.ispartofseries Clinical endocrinology en
dc.rights Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. Details obtained from http://www.sherpa.ac.uk/romeo/issn/0300-0664/ http://olabout.wiley.com/WileyCDA/Section/id-820227.html en
dc.rights.uri https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm en
dc.title Evolution of Paget's disease of bone in adults inheriting SQSTM1 mutations en
dc.type Journal Article en
dc.identifier.doi 10.1111/cen.12741 en
pubs.issue 3 en
pubs.begin-page 315 en
pubs.volume 83 en
dc.rights.holder Copyright: John Wiley & Sons en
dc.identifier.pmid 25664955 en
pubs.author-url http://onlinelibrary.wiley.com/doi/10.1111/cen.12741/abstract en
pubs.declined 2015-12-03T13:20:14.61+1300 en
pubs.deleted 2015-12-03T13:20:14.693+1300 en
pubs.end-page 319 en
pubs.publication-status Published en
dc.rights.accessrights http://purl.org/eprint/accessRights/RestrictedAccess en
pubs.subtype Article en
pubs.elements-id 475824 en
pubs.org-id Medical and Health Sciences en
pubs.org-id School of Medicine en
pubs.org-id Medicine Department en
dc.identifier.eissn 1365-2265 en
pubs.record-created-at-source-date 2015-12-02 en
pubs.dimensions-id 25664955 en

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