title: Epidemiogenetic study of French families with Paget's disease of bone.
abstract: OBJECTIVE
  To search for association with environmental factors and to determine SQSTM1/p62 mutations prevalence in French families with Paget's disease of bone (PDB).
  
  
  METHODS
  Unrelated patients with a confirmed diagnosis of PDB were recruited in three Rheumatology departments and informed consent obtained. First- and second-degree relatives of each index case had a physical examination, blood taken for DNA extraction and biochemical measurements, and a whole-body bone scan. Exons 7 and 8 and exon-intron boundaries of SQSTM1/p62 (p62) gene were PCR-amplified before sequencing. Haplotype carriers of the p62(P392L) mutation were determined. Comparisons between PDB patients and healthy relatives were performed.
  
  
  RESULTS
  We investigated 18 families consisting of 83 individuals: 20 patients with known PDB, three relatives with newly-diagnosed PDB and 60 healthy relatives. Index cases and/or relatives with Dupuytren's disease were found in eight (44.4%) out of the 18 families. Forty-three percent of PDB patients were former or current tobacco users versus 18% of healthy relatives (P=0.02; OR=3.37 (1.04-11.09)). Five index cases (27.8%) were carriers of SQSTM1/p62 mutations: three p62(P392L) mutations, one p62(P392L/A390X) double mutation and one p62(A390X) mutation. The p62(P392L) mutation was carried by haplotype 2 in all four index cases.
  
  
  CONCLUSIONS
  Accurate phenotypic assessment of PDB patients' relatives allowed for diagnosing PDB in three asymptomatic relatives. There was evidence for an aggregation of Dupuytren's disease in PDB families (not associated with SQSTM1/p62 mutation), and for an association between PDB and tobacco use. Half of PDB familial forms carried a SQSTM1/p62 mutation, p62(P392L) mutation being the most frequent.
authors.affiliation: Department of Medicine, Laval University, and Division of Rheumatology, CHUQ-CHUL, Quebec City, Quebec, Canada. laetitia.michou@crchul.ulaval.ca
authors.forename: Laëtitia
authors.initials: L
authors.lastname: Michou
authors.forename: Corinne
authors.initials: C
authors.lastname: Collet
authors.forename: Jean
authors.initials: J
authors.lastname: Morissette
authors.forename: Maurice
authors.initials: M
authors.lastname: Audran
authors.forename: Thierry
authors.initials: T
authors.lastname: Thomas
authors.forename: Edith
authors.initials: E
authors.lastname: Gagnon
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Launay
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Laplanche
authors.forename: Jacques P
authors.initials: JP
authors.lastname: Brown
authors.forename: Philippe
authors.initials: P
authors.lastname: Orcel
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D050071:Bone Density Conservation Agents / Q000627:therapeutic use; D015897:Comorbidity; D004252:DNA Mutational Analysis; D004387:Dupuytren Contracture / Q000453:epidemiology; D005190:Family; D005192:Family Health; D005260:Female; D005602:France / Q000453:epidemiology; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D017720:Molecular Epidemiology; D009154:Mutation; D010001:Osteitis Deformans / Q000188:drug therapy / Q000453:epidemiology* / Q000235:genetics*; D012307:Risk Factors; D000071456:Sequestosome-1 Protein; D014029:Tobacco Use Disorder / Q000453:epidemiology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D050071:Bone Density Conservation Agents; C099718:SQSTM1 protein, human; D000071456:Sequestosome-1 Protein