Paget's Disease of Bone: Evidence for a Susceptibility Locus on Chromosome 18q and for Genetic Heterogeneity

@article{Haslam1998PagetsDO,
  title={Paget's Disease of Bone: Evidence for a Susceptibility Locus on Chromosome 18q and for Genetic Heterogeneity},
  author={Sonya Haslam and Wim Van Hul and A Morales-Piga and Wendy Balemans and Jos{\'e} L. San-Mill{\'a}n and Kiyoshi Nakatsuka and Patrick J. Willems and Neva E. Haites and Stuart H. Ralston},
  journal={Journal of Bone and Mineral Research},
  year={1998},
  volume={13}
}
Paget's disease of bone is a common condition characterized by bone pain, deformity, pathological fracture, and an increased incidence of osteosarcoma. Genetic factors play a role in the pathogenesis of Paget's disease but the molecular basis of the disease remains unclear. Previous genetic linkage studies have mapped the rare Paget's disease‐like bone dysplasia familial expansile osteolysis (FEO) to chromosome 18q21–22, and recent work has shown evidence of linkage between this locus and Paget… Expand
Familial Paget's disease of bone: patterns of inheritance and frequency of linkage to chromosome 18q.
TLDR
These studies confirm the presence of genetic heterogeneity in familial Paget's disease but show that linkage of the disease to the previously identified candidate locus on chromosome 18q21-22 is relatively uncommon. Expand
Familial Paget's Disease of Bone: Nonlinkage to the PDB1 and PDB2 Loci on Chromosomes 6p and 18q in a Large Pedigree
  • D. Good, F. Busfield, +4 authors J. Shaw
  • Medicine
  • Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
  • 2001
TLDR
The hypothesis is that a novel susceptibility gene relevant to the pathogenesis of Paget's disease of bone lies elsewhere in the genome in the affected members of this pedigree and will be identified using a microsatellite genomewide scan followed by positional cloning. Expand
Variable disease severity associated with a paget's disease predisposition gene
TLDR
The identification of a region on the long arm of chromosome 18 that carries a predisposition gene for Paget's disease using linkage analysis implies that the age of onset is highly variable for this locus, indicating variable expression of disease in individuals carrying the same mutation. Expand
Inheritance of osteosarcoma and Paget's disease of bone: a familial loss of heterozygosity study.
TLDR
A father and son, their young ages at diagnosis of Pagetoid sarcoma, the identical sites of disease involvement, and a loss of heterozygosity study illustrating the inheritance of the presumed defective gene are described. Expand
Paget disease of bone: mapping of two loci at 5q35-qter and 5q31.
TLDR
The mapping of two novel loci for Paget disease of bone are demonstrated and proposed, providing further evidence for genetic heterogeneity of this highly prevalent disorder. Expand
Evidence for a novel osteosarcoma tumor-suppressor gene in the chromosome 18 region genetically linked with Paget disease of bone.
TLDR
Findings suggest that the association between Paget disease and osteosarcoma is the result of a single gene or two tightly linked genes on chromosome 18, which is the second most common metabolic bone disease after osteoporosis. Expand
Genomewide search in familial Paget disease of bone shows evidence of genetic heterogeneity with candidate loci on chromosomes 2q36, 10p13, and 5q35.
TLDR
A genomewide search in 319 individuals with familial PDB indicated the presence of several susceptibility loci for PDB and identified a strong candidate locus for the disease, on chromosome 5q35. Expand
Genetics of Paget's disease of bone
TLDR
Improved understanding of bone biology and the causes of Paget’s disease raises the prospect that genetic profiling could identify patients at high risk of developing complications, permitting enhanced surveillance and early therapeutic intervention. Expand
Mutation Screening of the TNFRSF11A Gene Encoding Receptor Activator of NFkB (RANK) in Familial and Sporadic Paget's Disease of Bone and Osteosarcoma
TLDR
Mutation screening of the TNFRSF11A gene in patients with familial and sporadic Paget's disease as well as DNA extracted from Pagetic bone lesions, an osteosarcoma arising in PageticBone and six osteosARcoma cell lines indicate that TNFRL11A mutations contribute neither to the vast majority of cases of sporadic or familial PDB, nor to the development of osteosArcoma. Expand
A Familial Loss of Heterozygosity Study
TLDR
A father and son, their young ages at diagnosis of Pagetoid sarcoma, the identical sites of disease involvement, and a loss of heterozygosity study illustrating the inheritance of the presumed defective gene are described. Expand
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References

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Genetic linkage of Paget disease of the bone to chromosome 18q.
TLDR
A large kindred with a high incidence of Paget disease was examined to determine if it was linked to genetic markers in the same region of chromosome 18 as that for familial expansile osteolysis, and a two-point LOD score of 3.40 demonstrated that the gene(s) responsible for FEO and that for Paget Disease are either closely linked or the same locus. Expand
A family study of Paget's disease of bone.
TLDR
Overall, the findings were consistent with the hypothesis that Paget's disease is caused by infection with a common and widespread virus superimposed on genetic variation for susceptibility and perhaps severity of the disease. Expand
Genetic linkage of familial expansile osteolysis to chromosome 18q.
TLDR
Mapping a new locus for a gene involved in regulation of bone metabolism may also have implications in the study of Paget's disease of bone which is a common related bone dysplasia. Expand
Familial Aggregation of Paget's Disease of Bone
This epidemiologic study of Paget's disease of bone used data from 788 cases and 387 spouse controls to investigate the following: (1) the extent to which this disorder aggregates in families; (2)Expand
Frequency and characteristics of familial aggregation of paget's disease of bone
TLDR
The data support the existence of two distinct subtypes of Paget's disease of bone, which appears to be transmitted via both paternal and maternal sides, and pedigree analysis suggested an autosomal dominant inheritance or multifactorial mechanism. Expand
Familial expansile osteolysis.
TLDR
Familial expansile osteolysis is a unique bone dysplasia, which has, over five generations, affected 42 members of a Northern Ireland family and most affected members of the family have an associated early-onset deafness and loss of dentition as a result of unique middle ear and dental abnormalities. Expand
Does Paget's Disease Really Have a Viral Aetiology? Letter to the Editor: Maybe Not
The recent paper by Reddy et al. draws attention to their finding of measles virus transcripts by RT/PCR in peripheral blood cells and bone marrow from Pagetic patients, but fails to acknowledge orExpand
Evidence for secular change in Paget's disease.
TLDR
It is demonstrated that, on average, newly referred patients with Paget's disease have less severe disease and are significantly older at diagnosis than was the case two decades ago. Expand
Heritable Disorders of Connective Tissue
TLDR
The remainder of the book is devoted to detailed clinical descriptions of the rare syndromes previously enumerated, together with a full account of what is known of their mode of inheritance. Expand
European distribution of Paget's disease of bone.
The prevalence of Paget's disease of bone was mapped from 1416 replies to a postal questionnaire sent to radiologists throughout Western Europe. Subsequently radiological surveys were carried out inExpand
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