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 p62P392L 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 p62P392L mutations, one p62P392L/A390X double mutation and one p62A390X mutation. The p62P392L mutation was carried by haplotype 2 in all four index cases.
Conclusion
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, p62P392L mutation being the most frequent.
