Paget's disease of bone—genetic and environmental factors
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KEY POINTS * The prevalence of Paget's disease has decreased in many countries * A large number of patients have a family history of Paget's disease * Mutations in _SQSTM1_ (which
encodes sequestosome-1) account for the susceptibility to develop Paget's disease in some families * Some studies in patients with Paget's disease and in transgenic mice support
the involvement of measles virus in the aetiology of the disorder * The availability of effective measles vaccines since 1963 might explain the decrease in diagnosis of Paget's disease
in a number of countries ABSTRACT Paget's disease of bone is generally diagnosed in individuals aged >50 years, usually manifests in one or several bones and is initiated by
osteoclast-induced osteolytic lesions. Subsequently, over a period of many years, osteoblastic activity can result in sclerosis and deformation of bone. The prevalence of Paget's
disease is highest in the UK and in countries where a large number of residents have ancestors from the UK. Currently, in many countries, the prevalence of the disorder has decreased. A
considerable number of affected patients have a family history of Paget's disease and the disorder has an autosomal dominant pattern of inheritance but with incomplete penetrance. A
large number of mutations in SQSTM1 (which encodes sequestosome-1; also known as ubiquitin-binding protein p62) seem to account for the susceptibility to develop Paget's disease in some
families; the involvement of other genes is currently under investigation. In addition to a genetic cause, environmental factors have been proposed to have a role in the pathogenesis of
Paget's disease. Although most evidence has been presented for measles virus as an aetiologic factor, some studies have not confirmed its involvement. The decreasing incidence of
Paget's disease, which could be attributed to measles vaccination along with the measles virus nucleocapsid protein induction of Paget's disease lesions in transgenic mice,
supports an aetiologic role of the virus. Access through your institution Buy or subscribe This is a preview of subscription content, access via your institution ACCESS OPTIONS Access
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subscriptions * Read our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS A MUTATION IN THE _ZNF687_ GENE THAT IS RESPONSIBLE FOR THE SEVERE FORM OF PAGET’S DISEASE OF
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Berry, E. Moreno and D. Marzese for technical support, and Eli and Edythe Broad and Lois Rosen for grant support. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * John Wayne Cancer Institute,
Providence Saint Johns Health Center, 2200 Santa Monica Boulevard, Santa Monica, 90404, CA, USA Frederick R. Singer Authors * Frederick R. Singer View author publications You can also search
for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to Frederick R. Singer. ETHICS DECLARATIONS COMPETING INTERESTS The author declares no competing financial
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ARTICLE Singer, F. Paget's disease of bone—genetic and environmental factors. _Nat Rev Endocrinol_ 11, 662–671 (2015). https://doi.org/10.1038/nrendo.2015.138 Download citation *
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