Genetic Study of Families Affected by Paget's Disease of Bone

NCT00747994 | Completed

• 1 other identifier: P070203
• Study Type: observational
• Target: 83
• Locations: 1 country
• Sites: 1

Brief Summary

Paget's disease of bone is a frequent bone disorder which usually starts after the age of 40 and which is characterized by bone pain and deformities. Although often without any symptoms, this disease may have severe complications such as fissures, fractures, neurological compression, or deafness. In some cases, it is a genetic disorder transmitted with a dominant autosomal pattern of inheritance: one of the two parents carrying the disease transmits it to his offspring with a risk of 50% for each child. Since 2002, the first gene involved in Paget's disease of bone is known and 14 mutations of this gene have been published. A study confirmed that the presence of those mutations was associated with younger age of onset and more extensive disease. Thus, the knowledge of those genetic factors in the relatives of an affected individual allows the screening of the patients with a higher risk for complications, who may benefit from a medical follow up and earlier treatment, in order to avoid complications. Indeed, Paget's disease of bone may be treated efficiently by bisphosphonates. This project aims at identifying and collecting over one year, 15 affected individuals affected by Paget's disease of bone and the relatives up to the second degree of relativeness (a total of 100 individuals is expected). The blood samples may be analysed in order to search for mutations of the previously known gene and/or to search for new mutations on new genes.

Conditions

Paget's Disease of Bone

Keywords

Paget's disease of bone; Relatives; Mutations screening; Haplotypes analysis; Linkage analysis; < 55 years; 4 > or = WAFFECTED Bones; bone deformity

Outcome Measures

Primary Outcomes (1)

• To identify new mutations or new haplotypes of mutations already identified, and/or to identify new mutations in new genes of Paget's disease of bone.

  2007-2008

Study Arms (1)

1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

15 patients affected by Paget's disease of bone and their relatives at the first or second degree of relativeness total of about 100 individuals

You may qualify if:

• Patient aged over 18 years,
• patient who underwent a clinical examination,
• patient who gave its written consent,
• Each individual (index case) affected by Paget's disease of bone (with diagnosis confirmed by alkalies phosphatases analysis and/or imaging with bone scintigraphy and radiographies on the affected sites with a typical aspect of the disease), and :
• At least one relative affected by Paget's disease of bone with confirmed diagnosis (see above),
• Or an age at diagnosis \< 55 years,
• Or a polyostotic involvement with at least 4 affected bones,
• Or the presence of a bone deformity at the time of the diagnosis.
• Each relative with established phenotype by imaging (bone scintigraphy and/or radiographies), at first or second degree of relativeness of an index case defined in (a).

You may not qualify if:

• Index case with not confirmed Paget's disease of bone by biological and/or radiological examinations,
• Index with confirmed Paget's disease but without relative with the same disease, with an age at diagnosis \>55 years, with a number of affected bones \<4, without any bone deformity at the time of the diagnosis
• Healthy relatives of a Paget patient who refuse to undergo bone scintigraphy and bone radiographies.
• Individuals \< 18 years
• Pregnant or breast
• feeding woman-individual living ina sanitary or social establishment
• individual under guardianship
• individual in an emergency situation
• individual unable to give his consent
• incarcerated individual
• patient not covered by healthcare institutions

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead
• Novartis: collaborator
• Association Rhumatisme et Travail: collaborator

Study Sites (1)

CHU Lariboisière

Paris, Île-de-France Region, 75010, France

Location

Related Publications (2)

• Collet C, Michou L, Audran M, Chasseigneaux S, Hilliquin P, Bardin T, Lemaire I, Cornelis F, Launay JM, Orcel P, Laplanche JL. Paget's disease of bone in the French population: novel SQSTM1 mutations, functional analysis, and genotype-phenotype correlations. J Bone Miner Res. 2007 Feb;22(2):310-7. doi: 10.1359/jbmr.061106.

  PMID: 17129171 BACKGROUND

• Morissette J, Laurin N, Brown JP. Sequestosome 1: mutation frequencies, haplotypes, and phenotypes in familial Paget's disease of bone. J Bone Miner Res. 2006 Dec;21 Suppl 2:P38-44. doi: 10.1359/jbmr.06s207.

  PMID: 17229007 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

collection of extracted DNA, RNA and serum samples and urinary samples

MeSH Terms

Conditions

Osteitis Deformans

Condition Hierarchy (Ancestors)

Bone Diseases; Musculoskeletal Diseases

Study Officials

• Laetitia Michou, MD PhD

  CHU Lariboisière

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: FAMILY BASED
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: September 5, 2008
• First Posted: September 8, 2008
• Study Start: September 1, 2007
• Primary Completion: September 1, 2008
• Study Completion: September 1, 2008
• Last Updated: July 13, 2010

Record last verified: 2010-07

Locations

FR (1)