To search for association with environmental factors and to determine SQSTM1/p62 mutations prevalence in French families with Paget’s disease of bone (PDB).

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.

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.

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.