Clinical Trial: Genetic Study of Families Affected by Paget's Disease of Bone
Study Status: Completed
Recruit Status: Completed
Study Type: Observational
Official Title: Genetic Study of Families Affected by Paget's Disease of Bone
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.
Detailed Summary:
Background : Paget's disease of bone is a chronic bone disorder with a late onset, usually after the age of 40. This disease is transmitted on a dominant autosomal pattern of inheritance with incomplete penetrance. Since 2002, the first gene (SEQUESTOSOME 1 or SQSTM1) involved in Paget's disease of bone is known. Actually, 14 mutations of this gene located in exons 7 and 8 have been reported in familial forms of the disease as well as in sporadic forms. Although the size of the samples studied in the literature are rather small to establish phenotype genotype correlations, it seems that the presence of those mutations are associated with an earlier onset of the disease and a more extensive disease. However, the presence of those mutations seems not sufficient to explain the whole development of the disease, but functional analyses may help to understand the real effect of those mutations. The link between the genetics and the observation of PARANYXOVIRAL inclusions in the nucleus of osteoclasts is not actually established. The hypothesis of an interaction between gene and environment may be plausible for several authors.
The results of a study on 94 sporadic French patients with Paget's disease of bone lead to the identification of two new mutations of SQSTM1 gene and showed the presence of double SQSTM1 mutations. This study established phenotype genotype correlations, affected individuals who carry a mutation have a younger age at diagnosis and a polyostotic involvement. This phenotype genotype correlation is a major element that may help to target the relatives at risk for complications, who may benefit from an earlier treatment to prevent complications occurrence.
Primary objective : to recruit 15 patients affected by Paget's disease of bone, with a familial form, and their relatives healthy or affected, up to the seco
Sponsor: Assistance Publique - Hôpitaux de Paris
Current Primary Outcome: 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. [ Time Frame: 2007-2008 ]
Original Primary Outcome: Same as current
Current Secondary Outcome:
Original Secondary Outcome:
Information By: Assistance Publique - Hôpitaux de Paris
Dates:
Date Received: September 5, 2008
Date Started: September 2007
Date Completion:
Last Updated: July 12, 2010
Last Verified: July 2010
