Genetic linkage of Paget disease of the bone to chromosome 18q

J. D. Cody, F. R. Singer, G. David Roodman, B. Otterund, T. B. Lewis, M. Leppert, R. J. Leach

Research output: Contribution to journalArticle

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Abstract

Paget disease is a common bone disease characterized by abnormal osteoclasts that are large, multinucleated, and overactive and that contain paramyxovirus-like nuclear inclusions. There is evidence for a major genetic component to Paget disease, with up to 40% of patients having affected first- degree relatives; however, the locus (loci) and gene(s) involved are unknown. Another bone disorder, familial expansile osteolysis (FEO), although extremely rare, also is characterized by similar osteoclast abnormalities but has an earlier age at onset and a more aggressive clinical progression. The causative gene for FEO has been localized to a region of human chromosome 18q. On the basis of the presence of similar clinical findings and of vital- like nuclear inclusions in osteoclasts, we hypothesized that FEO and Paget disease are allelic versions of the same locus. Therefore, a large kindred with a high incidence of Paget disease was examined to determine if Paget disease was linked to genetic markers in the same region of chromosome 18 as that for FEO. Our analysis yielded a two-point LOD score of 3.40, with the genetic marker D18S42, a marker tightly linked to the FEO locus. This demonstrates that the gene(s) responsible for FEO and that for Paget disease are either closely linked or the same locus.

Original languageEnglish (US)
Pages (from-to)1117-1122
Number of pages6
JournalAmerican Journal of Human Genetics
Volume61
Issue number5
DOIs
StatePublished - Nov 1997
Externally publishedYes

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Osteitis Deformans
Genetic Linkage
Chromosomes
Osteoclasts
Intranuclear Inclusion Bodies
Genetic Markers
Genes
Chromosomes, Human, Pair 18
Bone Diseases
Human Chromosomes
Age of Onset
Hereditary expansile Polyostotic osteolytic dysplasia
Bone and Bones
Incidence

ASJC Scopus subject areas

  • Genetics

Cite this

Cody, J. D., Singer, F. R., Roodman, G. D., Otterund, B., Lewis, T. B., Leppert, M., & Leach, R. J. (1997). Genetic linkage of Paget disease of the bone to chromosome 18q. American Journal of Human Genetics, 61(5), 1117-1122. https://doi.org/10.1086/301601

Genetic linkage of Paget disease of the bone to chromosome 18q. / Cody, J. D.; Singer, F. R.; Roodman, G. David; Otterund, B.; Lewis, T. B.; Leppert, M.; Leach, R. J.

In: American Journal of Human Genetics, Vol. 61, No. 5, 11.1997, p. 1117-1122.

Research output: Contribution to journalArticle

Cody, JD, Singer, FR, Roodman, GD, Otterund, B, Lewis, TB, Leppert, M & Leach, RJ 1997, 'Genetic linkage of Paget disease of the bone to chromosome 18q', American Journal of Human Genetics, vol. 61, no. 5, pp. 1117-1122. https://doi.org/10.1086/301601
Cody, J. D. ; Singer, F. R. ; Roodman, G. David ; Otterund, B. ; Lewis, T. B. ; Leppert, M. ; Leach, R. J. / Genetic linkage of Paget disease of the bone to chromosome 18q. In: American Journal of Human Genetics. 1997 ; Vol. 61, No. 5. pp. 1117-1122.
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