title: Novel SQSTM1 mutations in patients with Paget's disease of bone in an unrelated multiethnic American population.
abstract: More than 20 mutations of the Sequestosome 1 (SQSTM1) gene have been reported in patients of European descent affected by Paget's disease of bone (PDB). In this investigation, a systematic screening for SQSTM1 mutations was conducted in consecutively evaluated unrelated patients with phenotypical PDB living in the New York City area (NY, United States). Seventy unrelated PDB patients with a multiethnic background, mostly of Jewish, Italian American, and Western European ancestries, were recruited. Sequencing of exons 7 and 8 was performed on DNA samples isolated from peripheral blood. Seven patients (10%) had SQSTM1 mutations, of which three had a family history of PDB. Four patients carried the C1215T (P392L) mutation, and three patients carried novel SQSTM1 missense mutations: T1085A (S349T), C1209T (A390V), and T1290A (L417Q) mutations. All PDB patients with SQSTM1 mutations had polyostotic involvement, and the mean number of affected bones was significantly higher in pagetic patient carriers of a SQSTM1 mutation when compared to non-mutated PDB patients (4.0 vs. 2.0, respectively; P = 0.003). Haplotype analysis in patient carriers of the P392L mutation revealed that all P392L mutations were carried by haplotype 2. The SQSTM1 mutation rate in unrelated American patients described in the present study was similar to that reported in European populations.
authors.affiliation: Department of Medicine, Laval University, CHUQ (CHUL) Research centre and Division of Rheumatology, CHUQ (CHUL), Quebec City, QC, Canada. laetitia.michou@crchul.ulaval.ca
authors.forename: Laëtitia
authors.initials: L
authors.lastname: Michou
authors.forename: Jean
authors.initials: J
authors.lastname: Morissette
authors.forename: Edith R
authors.initials: ER
authors.lastname: Gagnon
authors.forename: Anik
authors.initials: A
authors.lastname: Marquis
authors.forename: Maryann
authors.initials: M
authors.lastname: Dellabadia
authors.forename: Jacques P
authors.initials: JP
authors.lastname: Brown
authors.forename: Ethel S
authors.initials: ES
authors.lastname: Siris
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D019943:Amino Acid Substitution / Q000235:genetics; D001483:Base Sequence; D004252:DNA Mutational Analysis; D005006:Ethnicity / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D006239:Haplotypes / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D010001:Osteitis Deformans / Q000208:ethnology* / Q000235:genetics*; D000071456:Sequestosome-1 Protein; D014481:United States / Q000208:ethnology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C099718:SQSTM1 protein, human; D000071456:Sequestosome-1 Protein