Variable disease severity associated with a Paget's disease predisposition gene

Robin J. Leach, Frederick R. Singer, Jannine D. Cody, G. David Roodman

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

We have recently identified a region on the long arm of chromosome 18 that carries a predisposition gene for Paget's disease using linkage analysis. This region was explored because of earlier studies demonstrating the presence of a gene for another bone disorder, familial expansile osteolysis (FEO) within this region. FEO has many similarities to Paget's disease including osteoclast abnormalities and viral-like nuclear inclusions. Therefore, it was proposed that FEO and Paget's disease are disorders resulting from mutations at the same locus. For our linkage study, we utilized a large kindred with a high incidence of Paget's disease. The propositus in this family had polyostotic disease symptoms beginning at age 31. During the process of characterizing this family, four other family members were diagnosed with Paget's disease. One of the proband's siblings was asymptomatic but had high normal serum alkaline phosphatase levels; Paget's disease was identified only after bone scanning (at age 50). This implies that the predisposition gene does not consistently cause severe disease and raises a question concerning the mechanism of predisposition: Does the predisposition gene affect the age of onset and/or the severity of disease? To further explore this question, two individuals from this kindred, under age 30 and carrying the affected haplotype, were evaluated for early onset Paget's disease. No evidence of disease was observed after thorough evaluation. This implies that the age of onset is highly variable for this locus, indicating variable expression of disease in individuals carrying the same mutation.

Original languageEnglish (US)
Pages (from-to)17-20
Number of pages4
JournalJournal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
Volume14
Issue numberSUPPL. 2
StatePublished - 1999
Externally publishedYes

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Genes
Age of Onset
Chromosomes, Human, Pair 18
Bone and Bones
Intranuclear Inclusion Bodies
Mutation
Osteoclasts
Haplotypes
Alkaline Phosphatase
Siblings
Incidence
Serum
Hereditary expansile Polyostotic osteolytic dysplasia

ASJC Scopus subject areas

  • Surgery

Cite this

Variable disease severity associated with a Paget's disease predisposition gene. / Leach, Robin J.; Singer, Frederick R.; Cody, Jannine D.; Roodman, G. David.

In: Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, Vol. 14, No. SUPPL. 2, 1999, p. 17-20.

Research output: Contribution to journalArticle

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