title: Genetics of Paget's disease of bone.
abstract: Paget's disease of bone (PDB) is a common condition, which is characterised by focal areas of increased and disorganized bone remodeling. Genetic factors play an important role in the disease. In some cases, Paget's disease is inherited in an autosomal dominant manner and the most common cause for this is a mutation in the SQSTM1 gene. Other familial cases have been linked to the OPTN locus on Chromosome 10p13 and still other variants have been identified by genome wide association studies that lie within or close to genes that play roles in osteoclast differentiation and function. Mutations in TNFRSF11A, TNFRSF11B and VCP have been identified in rare syndromes with PDB-like features. These advances have improved understanding of bone biology and the causes of PDB. The identification of genetic markers for PDB also raises the prospect that genetic profiling could identify patients at high risk of developing complications, permitting enhanced surveillance and early therapeutic intervention.
authors.affiliation: Bone and Rheumatology Research Group, Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh, EH4 2XU, UK, stuart.ralston@ed.ac.uk.
authors.forename: Stuart H
authors.initials: SH
authors.lastname: Ralston
authors.forename: Omar M E
authors.initials: OM
authors.lastname: Albagha
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000251:Adenosine Triphosphatases / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006801:Humans; D026901:Membrane Transport Proteins; D009154:Mutation; D010001:Osteitis Deformans / Q000235:genetics*; D053244:Osteoprotegerin / Q000235:genetics; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000235:genetics; D000071456:Sequestosome-1 Protein; D035582:Transcription Factor TFIIIA / Q000235:genetics; D000074405:Valosin Containing Protein
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; D026901:Membrane Transport Proteins; C409460:OPTN protein, human; D053244:Osteoprotegerin; D053246:Receptor Activator of Nuclear Factor-kappa B; C099718:SQSTM1 protein, human; D000071456:Sequestosome-1 Protein; C505686:TNFRSF11A protein, human; C506030:TNFRSF11B protein, human; D035582:Transcription Factor TFIIIA; D000251:Adenosine Triphosphatases; C000614178:VCP protein, human; D000074405:Valosin Containing Protein