Genomes and Genes
Summary: A disease marked by repeated episodes of increased bone resorption followed by excessive attempts at repair, resulting in weakened, deformed bones of increased mass. The resultant architecture of the bone assumes a mosaic pattern in which the fibers take on a haphazard pattern instead of the normal parallel symmetry.
Publications230 found, 100 shown here
- Inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia is caused by mutant valosin-containing proteinGiles D J Watts
Division of Genetics, Children s Hospital Boston, 300 Longwood Avenue, Harvard Medical School, Boston, Massachusetts 02115, USA
Nat Genet 36:377-81. 2004..Identification of VCP as causing IBMPFD has important implications for other inclusion-body diseases, including myopathies, dementias and Paget disease of bone (PDB), as it may define a new common pathological ubiquitin-based pathway...
- Valosin-containing protein (VCP) is required for autophagy and is disrupted in VCP diseaseJeong Sun Ju
Department of Neurology, Washington University School of Medicine, St Louis, MO 63110, USA
J Cell Biol 187:875-88. 2009..These data implicate VCP in autophagy and suggest that impaired autophagy explains the pathology seen in IBMPFD muscle, including TDP-43 accumulation...
- TDP-43 mediates degeneration in a novel Drosophila model of disease caused by mutations in VCP/p97Gillian P Ritson
Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
J Neurosci 30:7729-39. 2010..We suggest that these findings are likely relevant to the pathogenic mechanism of a broad array of TDP-43 proteinopathies, including frontotemporal lobar degeneration and amyotrophic lateral sclerosis...
- Enhanced ATPase activities as a primary defect of mutant valosin-containing proteins that cause inclusion body myopathy associated with Paget disease of bone and frontotemporal dementiaAtsushi Manno
Laboratory of Functional Biology, Kyoto University Graduate School of Biostudies, Kyoto 606 8501, Japan
Genes Cells 15:911-22. 2010..Elevated ATPase activities, thus, may be a hidden primary defect causing IBMPFD pathological phenotypes, which would be revealed when abnormal proteins are accumulated, as typically observed in aging...
- Quantification of skeletal kinetic indices in Paget's disease using dynamic 18F-fluoride positron emission tomographyG J R Cook
Department of Nuclear Medicine, Royal Marsden Hospital, Sutton, Surrey, United Kingdom
J Bone Miner Res 17:854-9. 2002....
- SQSTM1 gene analysis and gene-environment interaction in Paget's disease of boneLuigi Gennari
Department of Internal Medicine, Endocrine Metabolic Sciences and Biochemistry, University of Siena, Siena, Italy
J Bone Miner Res 25:1375-84. 2010..84 +/- 2.5 versus 2.76 +/- 2.2, p < .05). Overall, these data suggest that animal-related factors may be important in the etiology of PDB and may interact with SQSTM1 mutations in influencing disease severity...
- Valosin containing protein associated inclusion body myopathy: abnormal vacuolization, autophagy and cell fusion in myoblastsJouni Vesa
Department of Pediatrics, Division of Genetics and Metabolism, University of California, Irvine, CA 92868, USA
Neuromuscul Disord 19:766-72. 2009....
- The multiple faces of valosin-containing protein-associated diseases: inclusion body myopathy with Paget's disease of bone, frontotemporal dementia, and amyotrophic lateral sclerosisAngele Nalbandian
Department of Pediatrics, Division of Genetics and Metabolism, 2501 Hewitt Hall, University of California Irvine, 2501 Hewitt Hall, Irvine, CA 92696, USA
J Mol Neurosci 45:522-31. 2011..In this review, we will explore the pathogenesis and clinical phenotype of IBMPFD caused by VCP mutations...
- Loss of ubiquitin-binding associated with Paget's disease of bone p62 (SQSTM1) mutationsJames R Cavey
School of Biomedical Sciences, University of Nottingham, Nottingham, United Kingdom
J Bone Miner Res 20:619-24. 2005..This suggests that SQSTM1 mutations predispose to PDB through a common mechanism that depends on loss of ubiquitin-binding by p62...
- Founder effect in different European countries for the recurrent P392L SQSTM1 mutation in Paget's Disease of BonePui Yan Jenny Chung
Department of Medical Genetics, University and University Hospital of Antwerp, Universiteitsplein 1, 2610, Wilrijk, Belgium
Calcif Tissue Int 83:34-42. 2008..The chance to obtain this result due to 33 independent mutation events is 3.97 x 10(-14), providing strong evidence for a founder effect of the P392L SQSTM1 mutation in Belgian, Dutch, and Spanish patients with PDB...
- Ubiquitin recognition by the ubiquitin-associated domain of p62 involves a novel conformational switchJed Long
School of Chemistry, Centre for Biomolecular Sciences, University of Nottingham, Nottingham NG7 2RD, United Kingdom
J Biol Chem 283:5427-40. 2008..The conformational switch observed on binding may represent a novel mechanism that underlies specificity in regulating signalinduced protein recognition events...
- Imbalances in p97 co-factor interactions in human proteinopathyVanesa Fernández-Sáiz
Department of Molecular Cell Biology, Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany
EMBO Rep 11:479-85. 2010..Our results suggest that imbalanced co-factor binding to p97 is a key pathological feature of IBMPFD and potentially of other proteinopathies involving p97...
- TDP-43 in the ubiquitin pathology of frontotemporal dementia with VCP gene mutationsManuela Neumann
Center for Neuropathology and Prion Research, Ludwig Maximilians University, Munich, Germany
J Neuropathol Exp Neurol 66:152-7. 2007..TDP-43 is a common pathologic substrate linking a variety of distinct patterns of FTLD-U pathology caused by different genetic alterations...
- Evidence for a novel osteosarcoma tumor-suppressor gene in the chromosome 18 region genetically linked with Paget disease of boneM J Nellissery
Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, Philadelphia, PA 19140, USA
Am J Hum Genet 63:817-24. 1998Paget disease of bone, or "osteitis deformans," is a bone disorder characterized by rapid bone remodeling resulting in abnormal bone formation...
- A novel mutation (K378X) in the sequestosome 1 gene associated with increased NF-kappaB signaling and Paget's disease of bone with a severe phenotypeSarah L Rea
Laboratory for Molecular Endocrinology, Western Australian Institute for Medical Research, University of Western Australia, Nedlands
J Bone Miner Res 21:1136-45. 2006..p62 mutants increased NF-kappaB activation and significantly potentiated osteoclast formation and bone resorption in human primary cell cultures...
- Paget disease of boneTim Cundy
Department of Medicine, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand
Trends Endocrinol Metab 19:246-53. 2008..Most observations seem to fit best with the idea that Paget disease behaves as a multifocal benign neoplasm...
- Genome-wide association study identifies variants at CSF1, OPTN and TNFRSF11A as genetic risk factors for Paget's disease of boneOmar M E Albagha
Rheumatic Diseases Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh, UK
Nat Genet 42:520-4. 2010..09 x 10(-13)) and with rs3018362 on 18q21 near the TNFRSF11A gene (P = 5.27 x 10(-13)). These studies provide new insights into the pathogenesis of PDB and identify OPTN, CSF1 and TNFRSF11A as candidate genes for disease susceptibility...
- Differential gene expression in cultured osteoblasts and bone marrow stromal cells from patients with Paget's disease of boneDorit Naot
Department of Medicine, University of Auckland, New Zealand
J Bone Miner Res 22:298-309. 2007..We identified several differentially regulated genes, and we suggest that these changes could lead to the formation of the lesions...
- Detection of canine distemper virus in 100% of Paget's disease samples by in situ-reverse transcriptase-polymerase chain reactionA P Mee
Bone Disease Research Centre, University Department of Medicine, Manchester Royal Infirmary, UK
Bone 23:171-5. 1998..These results provide additional proof that CDV is present within pagetic bone and further support the hypothesis that paramyxoviruses are involved in the etiopathology of Paget's disease...
- Clinical delineation and localization to chromosome 9p13.3-p12 of a unique dominant disorder in four families: hereditary inclusion body myopathy, Paget disease of bone, and frontotemporal dementiaM J Kovach
Division of Genetics and Metabolism, Department of Pediatrics, Southern Illinois University School of Medicine, Springfield, Illinois, USA
Mol Genet Metab 74:458-75. 2001..Hence, autosomal dominant inclusion body myopathy (HIBM), Paget disease of bone (PDB), and frontotemporal dementia (FTD) localizes to a 1.08-6.46 cM critical interval on 9p13.3-12 in the region of autosomal recessive IBM2...
- Guidelines on the management of Paget's disease of boneP L Selby
Department of Medicine, Manchester Royal Infirmary, Manchester, UK
Bone 31:366-73. 2002
- New knowledge on critical osteoclast formation and activation pathways from study of rare genetic diseases of osteoclasts: focus on the RANK/RANKL axisJ C Crockett
Bone and Musculoskeletal Research Programme, Division of Applied Medicine, School of Medicine and Dentistry, University of Aberdeen, AB25 2ZD, Aberdeen, UK
Osteoporos Int 22:1-20. 2011..We highlight areas that require further study, particularly in light of the pharmacological interest in targeting the RANK signalling pathway to treat diseases caused by excessive bone resorption...
- Paget's disease of bone in The Netherlands: a population-based radiological and biochemical survey--the Rotterdam StudyMarelise E M W Eekhoff
Department of Endocrinology and Metabolic Diseases, Leiden University Medical Center, Leiden, The Netherlands
J Bone Miner Res 19:566-70. 2004..Subjects with raised and normal ALP from a population cohort were matched (1 in 6, total 548), and radiographs were taken. ALP was an excellent marker of the disease (RR, 10.9), but the majority of those affected had normal ALP...
- Three novel mutations in SQSTM1 identified in familial Paget's disease of boneTeresa L Johnson-Pais
Department of Pediatrics, University of Texas Health Science Center, San Antonio, Texas 78229, USA
J Bone Miner Res 18:1748-53. 2003..Disruptions of the C-terminal domain of SQSTM1 seem to be a leading cause of familial PDB...
- Epidemiological, clinical, and genetic characteristics of Paget's disease of bone in a rural area of Calabria, Southern ItalyD Rendina
Department of Clinical and Experimental Medicine, Federico II University Medical School, Via S Pansini, 5 80131 Naples, Italy
J Endocrinol Invest 33:519-25. 2010..The prevalence of Paget's disease of bone (PDB) is unknown in peninsular Southern Italy, although an elevated clinical severity of the disease was reported in patients from Campania...
- Sequestosome 1 mutations in Paget's disease of bone in Australia: prevalence, genotype/phenotype correlation, and a novel non-UBA domain mutation (P364S) associated with increased NF-kappaB signaling without loss of ubiquitin bindingSarah L Rea
Laboratory for Molecular Endocrinology, Western Australian Institute for Medical Research and UWA Centre for Medical Research, University of Western Australia, Nedlands, Australia
J Bone Miner Res 24:1216-23. 2009..This suggests that increased NF-kappaB signaling, but not the impairment of ubiquitin binding, may be essential in the pathogenesis of PDB associated with SQSTM1 mutations...
- Genetic epidemiology of Paget's disease of bone in italy: sequestosome1/p62 gene mutational test and haplotype analysis at 5q35 in a large representative series of sporadic and familial Italian cases of Paget's disease of boneAlberto Falchetti
Department of Internal Medicine, University of Florence, Florence, Italy
Calcif Tissue Int 84:20-37. 2009..This may be helpful in estimating the true rate of de novo mutations. We confirm the data on the existence of both a mutational hotspot at the UBA domain of SQSTM1/p62 and a founder effect in the PDB population...
- Novel UBA domain mutations of SQSTM1 in Paget's disease of bone: genotype phenotype correlation, functional analysis, and structural consequencesLynne J Hocking
Department of Medicine and Therapeutics, University of Aberdeen, Aberdeen, United Kingdom
J Bone Miner Res 19:1122-7. 2004..Functional and structural analysis showed that disease severity was related to the type of mutation but was unrelated to the polyubiquitin-binding properties of the mutant UBA domain peptides...
- Late-onset autosomal dominant limb girdle muscular dystrophy and Paget's disease of bone unlinked to the VCP gene locusMichael Kottlors
Division of Neuropediatrics and Muscle Disorders, University Children s Hospital Freiburg, Freiburg, Germany
J Neurol Sci 291:79-85. 2010..The family presented here suggests that a yet-unknown genetic defect can give rise to an autosomal dominant myopathy with Paget's disease but without dementia...
- Common susceptibility alleles and SQSTM1 mutations predict disease extent and severity in a multinational study of patients with Paget's diseaseOmar M E Albagha
Rheumatic Diseases Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK
J Bone Miner Res 28:2338-46. 2013..It is possible that with further refinement, genetic profiling may be of clinical value in identifying individuals at high risk of severe disease who might benefit from enhanced surveillance and early intervention...
- Delayed development of Paget's disease in offspring inheriting SQSTM1 mutationsMark J Bolland
Department of Medicine, University of Auckland, New Zealand
J Bone Miner Res 22:411-5. 2007..At any given age, the offspring were less likely to be diagnosed with Paget's disease and had less severe disease than their parents...
- Identification and molecular characterization of a novel splice-site mutation (G1205C) in the SQSTM1 gene causing Paget's disease of bone in an extended American familyG Beyens
Department of Medical Genetics, University and University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Antwerp, Belgium
Calcif Tissue Int 79:281-8. 2006..PDB mutations that disrupt the function of the PEST domain of SQSTM1 have not been reported before, so probably the pathogenic effect of both transcripts resides in the disruption of the ubiquitin-binding properties of the protein...
- Indications for a genetic association of a VCP polymorphism with the pathogenesis of sporadic Paget's disease of bone, but not for TNFSF11 (RANKL) and IL-6 polymorphismsPui Yan Jenny Chung
Department of Medical Genetics, University of Antwerp, Antwerp, 2610, Belgium
Mol Genet Metab 103:287-92. 2011..e. TNFRSF11A, CSF1, OPTN and TM7SF4), independent effect of each gene region was found and the cumulative population attributable risk is 72.7%...
- A progressive translational mouse model of human valosin-containing protein disease: the VCP(R155H/+) mouseAngele Nalbandian
Department of Pediatrics, Division of Genetics and Metabolism, 2501 Hewitt Hall, University of California, Irvine, Irvine, California 92696, USA
Muscle Nerve 47:260-70. 2013..More recently, these mutations have been linked to 2% of familial amyotrophic lateral sclerosis (ALS) cases. A knock-in mouse model offers the opportunity to study VCP-associated pathogenesis...
- Domain-specific mutations in sequestosome 1 (SQSTM1) cause familial and sporadic Paget's diseaseLynne J Hocking
Department of Medicine and Therapeutics, University of Aberdeen, UK
Hum Mol Genet 11:2735-9. 2002..0001). These studies confirm that mutations affecting the ubiquitin-binding domain of SQSTM1 are a common cause of familial and sporadic Paget's disease of bone...
- The ivory vertebra signTravis S Graham
Department of Radiology, University of Colorado Health Sciences Center, 4200 E Ninth Ave, Denver, CO 80262 USA
Radiology 235:614-5. 2005
- Proteomic analysis of a drosophila IBMPFD model reveals potential pathogenic mechanismsHsin Tzu Chan
Institute of Bioinformatics and Structural Biology and Department of Medical Sciences, National Tsing Hua University, Hsinchu, Taiwan
Mol Biosyst 8:1730-41. 2012..The molecular analysis of IBMPFD disease may benefit from the proteomics approach which combines the advantages of high throughput analysis and the focus on protein levels...
- The S349T mutation of SQSTM1 links Keap1/Nrf2 signalling to Paget's disease of boneTao Wright
School of Biomedical Sciences, University of Nottingham, UK
Bone 52:699-706. 2013..Thus, SQSTM1-mediated dysregulation of the Keap1-Nrf2 axis, which could potentially lead to aberrant production of oxidative response genes, may contribute to disease aetiology in a subset of PDB patients...
- Osteitis deformans (Paget's disease) in a Burmese python (Python molurus bivittatus)--a case reportRosario Preziosi
Department of Veterinary Public Health and Animal Pathology, Alma Mater Studiorum, Universita di Bologna, Via Tolara di Sopra 50, I 40064 Ozzano Emilia BO, Italy
Vet J 174:669-72. 2007b>Osteitis deformans (Paget's disease of bone) is a chronic focal disorder of bone remodelling characterized by an initial increase in osteoclast-mediated bone resorption, with subsequent compensatory increase in new bone formation, ..
- Epidemiology of Paget's disease of bone: a systematic review and meta-analysis of secular changesLuis Corral-Gudino
Servicio de Medicina Interna, Hospital El Bierzo, Ponferrada, Leon, Spain
Bone 55:347-52. 2013..Several studies have suggested that the prevalence and severity of PDB have fallen in recent years. The magnitude of this trend and its globalization have not been well established...
- A randomized clinical trial comparing oral alendronate and intravenous pamidronate for the treatment of Paget's disease of boneJ P Walsh
Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands, WA 6009, Australia
Bone 34:747-54. 2004..In patients previously treated with pamidronate, alendronate is more effective...
- Familial Paget's disease in The Netherlands: occurrence, identification of new mutations in the sequestosome 1 gene, and their clinical associationsE W M Eekhoff
Department of Endocrinology and Metabolic Diseases, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands
Arthritis Rheum 50:1650-4. 2004..To estimate the occurrence of familial Paget's disease of bone in The Netherlands, to examine the prevalence of mutations of the sequestosome 1 gene (SQSTM1) in identified families, and to assess potential genotype-phenotype associations...
- Genetics of Paget's disease of boneAnna Daroszewska
Institute of Medical Sciences, University of Aberdeen Medical School, Aberdeen AB25 2ZD, UK
Clin Sci (Lond) 109:257-63. 2005....
- Mutations of SQSTM1 are associated with severity and clinical outcome in paget disease of boneMicaela Rios Visconti
Rheumatic Diseases Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom
J Bone Miner Res 25:2368-73. 2010....
- Novel VCP mutations in inclusion body myopathy associated with Paget disease of bone and frontotemporal dementiaG D J Watts
Division of Genetics, Children s Hospital Boston, Harvard Medical School, Boston, MA, USA
Clin Genet 72:420-6. 2007..These new mutations may cause structural changes in VCP and provide some insight into the functional effects of pathogenic mutations...
- Management of Paget's disease of boneA L Langston
Health Services Research Unit, University of Aberdeen, UK
Rheumatology (Oxford) 43:955-9. 2004....
- Paget's disease of bone: evidence for a susceptibility locus on chromosome 18q and for genetic heterogeneityS I Haslam
Department of Medicine and Therapeutics, University of Aberdeen, United Kingdom
J Bone Miner Res 13:911-7. 1998..Data from three families did not support evidence of linkage to 18q21-22 however, indicating that Paget's disease is genetically heterogeneous and suggests the presence of at least one additional locus which remains to be discovered...
- Clinical and molecular studies in a unique family with autosomal dominant limb-girdle muscular dystrophy and Paget disease of boneV E Kimonis
Department of Pediatircs, Southern Illinois University School of Medicine, Springfield 62794 9658, USA
Genet Med 2:232-41. 2000..To characterize the clinical features and perform linkage analysis of candidate loci in a large Illinois family with autosomal dominant limb-girdle muscular dystrophy (LGMD) and Paget disease of bone (PDB)...
- Inclusion body myopathy with Paget disease of bone and frontotemporal dementia linked to VCP p.Arg155Cys in a Korean familyEun Joo Kim
Department of Neurology, Pusan National University Hospital, Pusan National University School of Medicine and Medical Research Institute, Busan, Korea
Arch Neurol 68:787-96. 2011..Missense mutations in the valosin-containing protein (VCP) gene on chromosome 9p13.3-p12 cause inclusion body myopathy with Paget disease of bone and frontotemporal dementia (hereafter referred to as IBMPFD; OMIM 167320)...
- Genetics of bone diseases: Paget's disease, fibrous dysplasia, osteopetrosis, and osteogenesis imperfectaLaetitia Michou
Service de rhumatologie du CHUQ CHUL H1365, Departement de Medecine, Centre de Recherche du CHUQ CHUL, Universite Laval, 2705, boulevard Laurier, G1V 4G2, Quebec, Canada
Joint Bone Spine 78:252-8. 2011..The recent identification of mutations in the CRTAP, LEPRE1, and PPIB genes in recessive forms has radically changed the classification of osteogenesis imperfecta and generated new pathophysiological hypotheses...
- Clinical and genetic heterogeneity in chromosome 9p associated hereditary inclusion body myopathy: exclusion of GNE and three other candidate genesGiles D J Watts
Division of Genetics and Metabolism, Children s Hospital, Harvard Medical School, 300 Longwood Avenue, Fegan 5, Boston, MA 02115, USA
Neuromuscul Disord 13:559-67. 2003..Expression studies indicate that GNE has a tissue-specific splice pattern, with four splice variants. Mutation analysis in three other candidate genes (beta-tropomyosin, NDUFB6 and SMU1) did not identify any mutations...
- Two Australian families with inclusion-body myopathy, Paget's disease of bone and frontotemporal dementia: novel clinical and genetic findingsKishore R Kumar
Department of Neurology, Royal North Shore Hospital, St Leonards, NSW 2065, Australia
Neuromuscul Disord 20:330-4. 2010..Leu198Trp). Our findings broaden the phenotypic spectrum of IBMPFD and further emphasise the resemblance to amyotrophic lateral sclerosis in some cases...
- Valosin-containing protein and the pathogenesis of frontotemporal dementia associated with inclusion body myopathyJake B Guinto
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, 422 Curie Blvd, 605B Stellar Chance Building, Philadelphia, PA, 19104 6140, USA
Acta Neuropathol 114:55-61. 2007..In this report, we review current literature on IBMPFD, focusing on the pathology of the disease and the biology of VCP with respect to IBMPFD...
- Impact of p62/SQSTM1 UBA domain mutations linked to Paget's disease of bone on ubiquitin recognitionThomas P Garner
Centre for Biomolecular Sciences, School of Chemistry, University Park, University of Nottingham, Nottingham, U K
Biochemistry 50:4665-74. 2011....
- A Brazilian family with hereditary inclusion body myopathy associated with Paget disease of bone and frontotemporal dementiaR D Fanganiello
Centro de Estudos do Genoma Humano, Departamento de Genética e Biologia Evolutiva, Instituto de Biociencias, Universidade de Sao Paulo, SP, Brasil
Braz J Med Biol Res 44:374-80. 2011..Furthermore, the R93C mutation is likely to be associated with the penetrance of all the clinical symptoms of the triad...
- Characteristics and familial aggregation of Paget's disease of bone in ItalyDaniela Merlotti
Department of Internal Medicine, Endocrine Metabolic Sciences and Biochemistry, University of Siena, Siena, Italy
J Bone Miner Res 20:1356-64. 2005..Familial aggregation was observed in 15% of cases...
- Randomized, active-controlled study of once-weekly alendronate 280 mg high dose oral buffered solution for treatment of Paget's diseaseM Hooper
University of Sydney, 56 St Johns Ave, Gordon, NSW, 2072, Australia
Osteoporos Int 20:141-50. 2009..A once-weekly alendronate 280 mg oral buffered solution was compared with an alendronate 40 mg/day tablet. While both were similarly effective, the tablet appeared to be better tolerated in this study...
- Multicenter blinded analysis of RT-PCR detection methods for paramyxoviruses in relation to Paget's disease of boneStuart H Ralston
Rheumatic Diseases Unit, School of Molecular and Clinical Medicine, University of Edinburgh, Edinburgh, UK
J Bone Miner Res 22:569-77. 2007....
- Evidence for increased clinical severity of familial and sporadic Paget's disease of bone in Campania, southern ItalyDomenico Rendina
Department of Clinical and Experimental Medicine, Federico II University Medical School, Naples, Italy
J Bone Miner Res 21:1828-35. 2006..A prevalent involvement of the spine and the skull, the sites preferentially involved in giant cell tumors complicating Paget's disease, was also shown in familial cases from this geographical region...
- Effect of age and gender on the number and distribution of sites in Paget's disease of boneM J Haddaway
Department of Diagnostic Imaging, Robert Jones and Agnes Hunt Orthopaedic Hospital, Oswestry, Shropshire SY10 7AG, UK
Br J Radiol 80:532-6. 2007..The lesser involvement at the axial sites in monostotic disease may lead to overestimation of the decline in PDB based on abdominal radiographs...
- Canine distemper virus induces human osteoclastogenesis through NF-kappaB and sequestosome 1/P62 activationPeter L Selby
Vitamin D Research Group, University School of Medicine, Manchester Royal Infirmary, Oxford Road, Manchester, United Kingdom
J Bone Miner Res 21:1750-6. 2006..We studied the effects of CDV on osteoclastogenesis in vitro and showed that CDV had a dose-dependent effect on osteoclastogenesis, through a possible mechanism involving activation of NF-kappaB and sequestosome 1/p62...
- Non-isomerized C-telopeptide fragments are highly sensitive markers for monitoring disease activity and treatment efficacy in Paget's disease of bonePeter Alexandersen
Centre for Clinical and Basic Research, Ballerup, Denmark
J Bone Miner Res 20:588-95. 2005....
- Comparison of different intravenous bisphosphonate regimens for Paget's disease of boneDaniela Merlotti
Department of Internal Medicine, Endocrine, Metabolic Sciences, and Biochemistry, University of Siena, Siena, Italy
J Bone Miner Res 22:1510-7. 2007..Single neridronate and zoledronate infusion showed a similar efficacy in up to 90% of patients nonresponders to pamidronate...
- Prevalence of Paget's disease of bone in ItalyLuigi Gennari
Department of Internal Medicine, Endocrine Metabolic Sciences and Biochemistry, University of Siena, Siena, and Department of Radiology, U O A I S Giovanni Battista Hospital of Torino, Italy
J Bone Miner Res 20:1845-50. 2005..7% to 2.4%, were higher in males than in females, and slightly differed between the two towns. Unlike previous studies in populations of British descent, no secular trend for a decreasing prevalence emerged...
- Genetics of Paget's disease of boneLaetitia Michou
Clinical Genetics Unit, Hopital Lariboisiere, Paris, France
Joint Bone Spine 73:243-8. 2006..Detection of a mutation allows evaluation of family members to ensure early diagnosis of the disease before complications develop...
- Paget's disease of bone: the skeletal distribution, complications and quality of life as perceived by patientsM Seton
Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Bulfinch 165, 55 Fruit Street, Boston, MA 02114, USA
Bone 48:281-5. 2011..Paget's disease of bone (PDB) is a focal disorder of bone metabolism with overgrowth of affected bone resulting in the skeletal complications of this disease...
- Novel SQSTM1 mutations in patients with Paget's disease of bone in an unrelated multiethnic American populationLaetitia Michou
Department of Medicine, Laval University, CHUQ CHUL Research centre and Division of Rheumatology, CHUQ CHUL, Quebec City, QC, Canada
Bone 48:456-60. 2011..The SQSTM1 mutation rate in unrelated American patients described in the present study was similar to that reported in European populations...
- Gene expression profile in osteoclasts from patients with Paget's disease of boneLaetitia Michou
Department of Medicine, Laval University, Canada G1V 4G2
Bone 46:598-603. 2010..They also suggest that the SQSTM1 P392L mutation plays a role in PDB pathogenesis, even at early preclinical stages in healthy carriers of the P392L mutation...
- Linkage of Paget disease of bone to a novel region on human chromosome 18q23David A Good
Department of Diabetes and Endocrinology, Princess Alexandra Hospital, Brisbane, Australia
Am J Hum Genet 70:517-25. 2002..71, at marker D18S70. Our data are consistent with genetic heterogeneity within the pedigree and indicate that 18q23 harbors a novel susceptibility gene for PDB...
- Usefulness of biochemical markers of bone turnover in assessing response to the treatment of Paget's diseaseL Alvarez
Service of Clinical Biochemistry, Hospital Clinic, University of Barcelona, Barcelona, Spain
Bone 29:447-52. 2001..Data on biological variation are useful for assessing actual changes induced by treatment...
- The majority of the genetic risk for Paget's disease of bone is explained by genetic variants close to the CSF1, OPTN, TM7SF4, and TNFRSF11A genesPui Yan Jenny Chung
Department of Medical Genetics, University and University Hospital of Antwerp, 2610, Antwerp, Belgium
Hum Genet 128:615-26. 2010..The calculated cumulative population attributable risk of these four loci turned out to be about 67% in our two populations, indicating that most of the genetic risk for PDB is coming from genetic variants close to these four genes...
- Paget's disease of bone is not associated with common polymorphisms in interleukin-6, interleukin-8 and tumor necrosis factor alpha genesLuis Corral-Gudino
Servicio de Medicina Interna, RETICEF, Hospital Universitario de Salamanca, Los Montalvos s n, Salamanca, Spain
Cytokine 52:146-50. 2010..Cytokines, specially interleukin (IL)-6, play an important role in the differentiation and activation of osteoclasts and might be involved in osteoblast stimulation in Paget's disease of bone (PDB)...
- Insights into the pathogenesis of Paget's diseaseG David Roodman
University of Pittsburgh, School of Medicine Hematology Oncology, Pittsburgh, PA, USA
Ann N Y Acad Sci 1192:176-80. 2010..These studies suggest that both genetic and environmental factors contribute to PD...
- VCP/p97 is essential for maturation of ubiquitin-containing autophagosomes and this function is impaired by mutations that cause IBMPFDEmilie Tresse
Department of Developmental Neurobiology, St Jude Children s Research Hospital, Memphis, TN, USA
Autophagy 6:217-27. 2010..We conclude that VCP is essential for maturation of ubiquitin-containing autophagosomes and that defect in this function may contribute to IBMPFD pathogenesis...
- VCP disease associated with myopathy, Paget disease of bone and frontotemporal dementia: review of a unique disorderVirginia E Kimonis
Division of Genetics and Metabolism, Department of Pediatrics, University of California, Irvine, 101 The City Drive, ZOT 4482, Orange, CA 92868, USA
Biochim Biophys Acta 1782:744-8. 2008..Inclusions seen in the muscle, brain and heart in VCP disease contain ubiquitin, beta amyloid and TDP-43, also seen in other neurodegenerative disorders thus implicating common pathways in their pathogenesis...
- Pathological consequences of VCP mutations on human striated muscleChristian U Hübbers
Institute of Biochemistry I, University of Cologne, Cologne, Germany
Brain 130:381-93. 2007..The latter findings provide a novel link to VCP carbohydrate interactions in the complex pathology of IBMPFD...
- Structure of the ubiquitin-associated domain of p62 (SQSTM1) and implications for mutations that cause Paget's disease of boneBarbara Ciani
School of Chemistry, University Park, Nottingham NG7 2RD, United Kingdom
J Biol Chem 278:37409-12. 2003..Thus, phenotypically identical substitution and deletion mutations do not appear to predispose to PDB through a mechanism dependent on a common loss of ubiquitin chain binding by p62...
- Inclusion body myopathy-associated mutations in p97/VCP impair endoplasmic reticulum-associated degradationConrad C Weihl
Department of Neurology, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, MO 63110, USA
Hum Mol Genet 15:189-99. 2006..Undegraded mutant DeltaF508-CFTR also accumulates in these aggregates. We conclude that IBMPFD mutations in p97/VCP disrupt ERAD and that this may contribute to the pathogenesis of IBMPFD...
- Recent advances in understanding the molecular basis of Paget disease of boneA Goode
School of Biomedical Sciences, University of Nottingham Medical School, Queen s Medical Centre, Nottingham NG7 2UH, UK
J Clin Pathol 63:199-203. 2010....
- Mutation of the sequestosome 1 (p62) gene increases osteoclastogenesis but does not induce Paget diseaseNoriyoshi Kurihara
VA Pittsburgh Healthcare System, Research and Development, Pittsburgh, Pennsylvania 15240, USA
J Clin Invest 117:133-42. 2007....
- Paget disease of boneG David Roodman
Department of Medicine, Division of Hematology Oncology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15240, USA
J Clin Invest 115:200-8. 2005..In this review, the pathophysiology of PD and evidence for both a genetic and a viral etiology for PD will be discussed...
- Long-term control of bone turnover in Paget's disease with zoledronic acid and risedronateDavid Hosking
City Hospital, Nottingham, UK
J Bone Miner Res 22:142-8. 2007..This effect is largely independent of pretreatment disease activity and prior bisphosphonate therapy...
- The role of immune cells and inflammatory cytokines in Paget's disease and multiple myelomaLori A Ehrlich
Department of Medicine Hematology Oncology, University of Pittsburgh, Pittsburgh, PA 15240, USA
Immunol Rev 208:252-66. 2005..This article discusses the role of immune cells and inflammatory cytokines and chemokines in the increased OCL activity in PD and MM bone disease, as well as the potential role of interleukin-3 in the suppression of OBL activity in MM...
- Autosomal dominant inclusion body myopathy, Paget disease of bone, and frontotemporal dementiaVirginia E Kimonis
Division of Genetics, Children s Hospital Boston, Harvard Medical School, Boston, Massachusetts 02115, USA
Alzheimer Dis Assoc Disord 19:S44-7. 2005..Identification of VCP as the gene causing IBMPFD has important implications for understanding the pathogenesis of neurodegenerative disorders...
- Guidelines for the diagnosis and management of Paget's disease: a UK perspectivePeter L Selby
University Department of Medicine, Manchester Royal Infirmary, Manchester, United Kingdom
J Bone Miner Res 21:P92-3. 2006
- Is the prevalence of Paget's disease of bone decreasing?Tim Cundy
Department of Medicine, University of Auckland, Auckland, New Zealand
J Bone Miner Res 21:P9-13. 2006..Paget's disease has become less prevalent and patients are presenting later, with less severe disease than previously. These data suggest that environmental factors are important in the etiology of Paget's disease...
- Paget disease of bone: mapping of two loci at 5q35-qter and 5q31N Laurin
Molecular Endocrinology and Oncology Research Center, CHUL Research Center, Quebec, QC, Canada G1V 4G2
Am J Hum Genet 69:528-43. 2001..It is proposed that the 5q35-qter and 5q31 loci be named "PDB3" and "PDB4," respectively...
- Transfer of Paget's disease from one part of the skeleton to another as a result of autogenous bone-grafting: a case reportMoussa Hamadouche
Departments of Orthopaedic and Reconstructive Surgery, Hopital Cochin, 27 rue du Faubourg St Jacques, 75014 Paris, France
J Bone Joint Surg Am 84:2056-61. 2002
- Paget's disease in an archeological populationJ Rogers
Department of Rheumatology, Bristol Royal Infirmary, United Kingdom
J Bone Miner Res 17:1127-34. 2002..This is likely caused by the small sample size, but this is by far the greatest number of cases of PDB described in a single skeletal assemblage to date. The distribution of lesions within the skeleton is unchanged...
- Severe hypocalcemia following bisphosphonate treatment in a patient with Paget's disease of boneHeather E Whitson
GRECC, VA Medical Center, Durham, NC 27710, USA
Bone 39:954-8. 2006..Physicians should be aware of the potential for hypocalcemia when patients with polyostotic Paget's disease and markedly elevated indicators of bone remodeling are initiated on powerful anti-resorptive therapy...
- Genetic linkage of Paget disease of the bone to chromosome 18qJ D Cody
Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, TX 78284, USA
Am J Hum Genet 61:1117-22. 1997..40, with the genetic marker D18S42, a marker tightly linked to the FEO locus. This demonstrates that the gene(s) responsible for FEO and that for Paget disease are either closely linked or the same locus...
- An Italian family with inclusion-body myopathy and frontotemporal dementia due to mutation in the VCP geneTeresa Gidaro
Department of Neuroscience, Catholic University, L go A Gemelli 8, 00168 Rome, Italy
Muscle Nerve 37:111-4. 2008..Our study demonstrates that VCP mutations are found in patients of Italian background and may lead to a variable clinical phenotype even within the same kinship...
- [Italian guidelines for the diagnosis and treatment of Paget's disease of bone]S Adami
Reumatologia, Universita di Verona, Verona, Italia
Reumatismo 59:153-68. 2007..The document provides the most updated recommendations based primarily on the "evidence-based- medicine" but also on the Italian regulation for the diagnostic procedures and on the available medical treatments...
- Gene expression profiling in Paget's disease of bone: upregulation of interferon signaling pathways in pagetic monocytes and lymphocytesZsolt B Nagy
National Institute of Rheumatology and Physiotherapy, Budapest, Hungary
J Bone Miner Res 23:253-9. 2008..We found a significant overexpression of the genes of the IFN pathway along with a downregulation of tnf-alpha. Our result suggest that IFN-mediated signaling may play important roles in aberrant osteoclastogenesis of PD...
- Inclusion body myopathy and Paget disease is linked to a novel mutation in the VCP geneD Haubenberger
Department of Neurology, Medical University of Vienna, Vienna, Austria
Neurology 65:1304-5. 2005....
- Valosin-containing protein disease: inclusion body myopathy with Paget's disease of the bone and fronto-temporal dementiaConrad C Weihl
Department of Neurology, Washington University School of Medicine, Saint Louis, MO 63110, USA
Neuromuscul Disord 19:308-15. 2009....
- Characterization of a non-UBA domain missense mutation of sequestosome 1 (SQSTM1) in Paget's disease of boneDereen Najat
School of Biomedical Sciences, University of Nottingham, Nottingham, United Kingdom
J Bone Miner Res 24:632-42. 2009....
- A novel mutation in the VCP gene (G157R) in a German family with inclusion-body myopathy with Paget disease of bone and frontotemporal dementiaAtbin Djamshidian
Department of Neurology, Medical University of Vienna Währinger Gürtel 18 20, Vienna A 1097, Austria
Muscle Nerve 39:389-91. 2009..Two family members also showed signs of early hearing impairment, which was confirmed to be sensorineural in one person, a symptom not yet described in the context of IBMPFD...
- Transgenic mice expressing mutant forms VCP/p97 recapitulate the full spectrum of IBMPFD including degeneration in muscle, brain and boneSara K Custer
Department of Developmental Neurobiology, St Jude Children s Research, Hospital, Memphis, TN 38105, USA
Hum Mol Genet 19:1741-55. 2010..In vitro studies indicate that mutant VCP causes inappropriate activation of the NF-kappaB signaling cascade, which could contribute to the mechanism of pathogenesis in multiple tissues including muscle, bone and brain...
- A comparison of in situ hybridisation, reverse transcriptase-polymerase chain reaction (RT-PCR) and in situ-RT-PCR for the detection of canine distemper virus RNA in Paget's diseaseJudith A Hoyland
Laboratory Medicine Academic Group, University of Manchester, Stopford Building, Oxford Road, Manchester M13 9PT, UK
J Virol Methods 109:253-9. 2003..These findings also have wider implications for other studies investigating viral expression...
- Morbidity and mortality associated with Paget's disease of bone: a population-based studyRobert A Wermers
Division of Endocrinology, Metabolism and Nutrition, Department of Internal Medicine, College of Medicine, Mayo Clinic, Rochester, Minnesota 55905, USA
J Bone Miner Res 23:819-25. 2008..We examined morbidity and mortality associated with this condition in a large inception cohort of Olmsted County, MN, residents with a new diagnosis of Paget's disease from 1950 through 1994...
- Translational Studies in VCP Inclusion Body Myopathy with Paget Disease of BoneVirginia Kimonis; Fiscal Year: 2009..abstract_text> ..
- CLONING NOVEL GENES FOR PAGETS DISEASE AND OSTEOSARCOMAMarc Hansen; Fiscal Year: 2001DESCRIPTION (Adapted from the Applicant's Abstract): Paget's disease of bone, or osteitis deformans, is a bone disorder characterized by rapid bone remodeling, resulting in abnormal bone formation...
- Clinical & Molecular Analysis of Neuromuscular DisordersVirginia Kimonis; Fiscal Year: 2001..The suggested training will provide the PI with skills necessary to investigate the clinical and basic molecular pathogenesis of these disorders and aid in the development of novel treatment protocols. ..
- Characterizing the Role of VCP in Paget's Disease of the BoneGiles Watts; Fiscal Year: 2009..In part 2, I will test the hypothesis that it is a disruption of the basal macroautophagy pathway that is the underlying molecular lesion that causes Paget disease of bone. ..
- TWO X-LINKED GENES THAT REGULATE MINERAL HOMEOSTASISMichael Whyte; Fiscal Year: 2002....
- Genetic basis of myopathy with Paget disease of boneVirginia Kimonis; Fiscal Year: 2008..e. effect on ATPase activity, protein-protein interactions, and hexamer formation). Study the VCP specific pathways in C2C12 cell lines (stably transfected wt and R155H VCP) during differentiation and under stress conditions...
- GENE CAUSING PAGET & LIMB-GIRDLE MUSCULAR DYSTROPHYVirginia Kimonis; Fiscal Year: 2003..Delineation of the genetic component responsible for the LGMD/PDB phenotype should promise similar insight and facilitate in the design of novel treatment protocols for the two disorders. ..
- Characterization of Familial Myopathy & Paget DiseaseVirginia Kimonis; Fiscal Year: 2005..Elucidation of the genetic defect will help us understand the pathogenesis of this multifaceted disorder and hopefully result in specific therapy. ..
- INHIBITION OF OSTEOCLAST ACTIVITY BY OIP-1/HSCALSAKAMURI REDDY; Fiscal Year: 2008..abstract_text> ..
- FACTORS INFLUENCING BONE METABOLISMLawrence Raisz; Fiscal Year: 2008..In addition, signal transduction pathways for enhanced osteoclastogenesis will be examined. ..
- Remodeling Extracellular Matrix:Degradation of CollagenStephen Krane; Fiscal Year: 2008..We will analyze the skeletal and extraskeletal phenotype of mice with a null mutation in the "neutrophil" collagenase, MMP-8, another collagenase expressed in the skeleton, as well as mice with double null MMP-8/MMP-13. ..
- METABOLISM IN NORMAL AND OSTEOARTHRITIC CARTILAGEHenry Mankin; Fiscal Year: 2001..It is further speculated that the study of serine proteinases produced by OA cartilage may have strong implications for the management of this debilitating disease. ..
- MECHANISMS OF TNF RECEPTOR MEDIATED OSTEOCLASTOGENSISYousef Abu Amer; Fiscal Year: 2003..The specific aims of the proposal are (1) to determine the mechanisms by which p55r promotes osteoclastogenesis, and (2) to determine the mechanisms by which p75r suppresses osteoclastogenesis. ..
- Prevention of Postmenopausal Bone Loss with Nitric OxideSunil Wimalawansa; Fiscal Year: 2007..The study will also pave the way for the future, for providing more acceptable, affordable and cost- effective therapies for the prevention of postmenopausalosteoporosis. ..
- PATHOBIOLOGY OF THE OSTEOCLAST IN PAGETS DISEASEG Roodman; Fiscal Year: 2002..abstract_text> ..
- Mechanisms of Tau-Based NeurodegenerationMark Forman; Fiscal Year: 2005..This proposal will also facilitate my transition from a trainee to a fully independent experimental neuropathologist. ..
- Paget's Disease of Bone/Dysplasia:Advances/ChallengesG Roodman; Fiscal Year: 2006..to become aware of the effectiveness of the various drugs that can be used to treat the two disorders; 5.) to understand the role of surgery in managing the two disorders. ..
- OSTEOCLASTS FROM TRANSGENIC MICEG Roodman; Fiscal Year: 2009..Our long-term goal will be to characterize the role of ADAM8/a9b1 in the bone destruction which accompanies collagen induced arthritis, which will be started in grant year 5. ..
- DEVELOPMENTAL ASPECTS OF OSTEOCLAST FORMATION IN VITROG Roodman; Fiscal Year: 2005....
- Program Project Grant-Pathobiology of Paget's DiseaseG Roodman; Fiscal Year: 2007..The knowledge gained from this P01 grant will offer important insights for normal bone cell biology especially for understanding the paracrine regulation of osteoblasts by OCLs. ..