Background Paget’s disease of bone (PDB) is associated with a germline

Background Paget’s disease of bone (PDB) is associated with a germline mutation in /p62 (mutations and measles virus have been implicated. a role in defining phenotype and that this may become more visible in a well characterized cohort. Methods This is an observational study focused on a cohort of patients with PDB drawn from the New England Registry in whom environmental and family history has been catalogued linked to radiographic data. Of the 217 persons who were enrolled in the Registry 42 (19%) responded to a letter inviting them to participate in testing for the presence of the measles antibody and in genetic testing for the P392L mutation. Results The mean age of the cohort in 2001 was 70 years (range 55-79); 27 IL4R were men (64%). The measles antibody was found in all cases tested. Nine patients had the P392L mutation (21%) Clofibrate 2 with familial PDB. In these persons early diagnosis of disease and spinal stenosis marked the male phenotype only. European ancestry was noted in the minority of those with P392L mutation. Most deaths recorded occurred in the 9th decade Clofibrate of life or later. Conclusions Spinal stenosis emerges as a prominent phenotype in P392L + men with aging. In these 42 patients with PDB from the New England Registry most do not carry the P392L mutation and many do not have European ancestry. Exposure to measles was confirmed in the Clofibrate majority. mutation (P392L) and the musculoskeletal correlates in a remarkably diverse population of people Clofibrate with PDB from the New England Registry for PDB Boston MA. METHODS Study Population In 2001 the New England Registry for PDB (NE Registry) was founded in an effort to understand the demographics of this disease in the United States. Enrollment was voluntary. Recruitment depended on responses to information about the study mailed to members of the Paget Foundation (New York New York); on referrals from physicians in New England; and on patients willingness to participate who were seen at the Massachusetts General Hospital (MGH). Medical record searches through the Research Patient Data Registry at Partners (Boston MA) were used to identify patients as well and letters requesting participation were sent to their physicians. Recruitment closed in early 2005 as numbers of interested patients dwindled. We were able to capture 254 persons with confirmed PDB who completed the study questionnaire; in 217 of these imaging was available documenting the skeletal distribution of disease. The Partners Institutional Review Board (Boston MA) approved the study. Analyses In 2004 42 patients enrolled in the NE Registry responded to a letter inviting them to participate in this study which involved blood drawn for the genetic analysis (Sequenom) of the P392L mutation and the enzyme-linked immunosorbent assay (ELISA) for measles antibody. The primer for the P392L mutation has been previously described. 9 The patient DNA was isolated and the sequences analyzed at Harvard Partners Center for Genetics and Genomics High Throughput Sequenom Genotyping Facility Cambridge MA. The samples were de-identified prior to genetic analysis. Measles antibody testing was performed by the MGH Clinical Laboratory Services (VIDAS Measles IgG assay BIOMERIEUX SA France). We compared the P392L positive patients to the P392L negative patients. Formal statistics were not pursued because of the small sample size. Living status was documented when that information was available. RESULTS Forty-two patients from the NE Registry agreed to have blood drawn for genetic analysis of the P392L mutation and for measles antibody testing; 27 were men (64%). The mean age of the cohort at the time of enrollment was 72 (range 30-87 years). This was comparable to the mean age in the NE Registry in general 73.2 years but reflected a slightly higher proportion of male participants. Most participants in this study were born in New England towns with parents or grandparents who immigrated to the US during the early 20th century. Nine of the 42 patients (21%) tested positive for the P392L mutation; 7 were men 2 of whom (28%) had Clofibrate familial PDB. (Table I) The ancestry of the P392L group was striking in that 6 of the 9 patients (67%) were from eastern Mediterranean countries including Greece Albania Turkey and Lebanon. Age at diagnosis <50 years of age (67%) polyostotic disease and the evolution of spinal stenosis (56%) appeared more commonly in the men with this mutation. (Image 1 The initial diagnosis of PDB tended to be on the basis of radiographic findings in the P392L cohort (55%) rather than on the basis of pain or elevated serum alkaline.