Mutation Screening of the TNFRSF11A Gene Encoding Receptor Activator of NFkB (RANK) in Familial and Sporadic Paget's Disease of Bone and Osteosarcoma

2001 ◽  
Vol 68 (3) ◽  
pp. 151-155 ◽  
Author(s):  
A.B. Sparks ◽  
S.N. Peterson ◽  
C. Bell ◽  
B.J. Loftus ◽  
L. Hocking ◽  
...  
Keyword(s):  
Mutation Screening ◽  
Paget’S Disease ◽  
Paget's Disease ◽  
Paget’S Disease Of Bone ◽  
Paget's Disease Of Bone ◽  
Gene Encoding ◽  
Receptor Activator

scholarly journals Pattern of SQSTM1 Gene Variants in a Hungarian Cohort of Paget’s Disease of Bone

2020 ◽  
Author(s):  
Judit Donáth ◽  
Bernadett Balla ◽  
Márton Pálinkás ◽  
Rita Rásonyi ◽  
Gyula Vastag ◽  
...  
Keyword(s):  
Mutation Screening ◽  
Paget’S Disease ◽  
Paget's Disease ◽  
Paget’S Disease Of Bone ◽  
Gene Variants ◽  
Eastern European ◽  
Paget's Disease Of Bone ◽  
Genetic Studies ◽  
Mutation Status ◽  
Sequestosome 1

Abstract Paget’s disease of bone (PDB) is characterized by focal or multifocal increase in bone turnover. One of the most well-established candidate genes for susceptibility to PDB is Sequestosome 1 (SQSTM1). Mutations in SQSTM1 have been documented among Western-European, British and American patients with PDB. However, there is no information on SQSTM1 mutation status in PDB patients from the Central- and Eastern-European regions. In this study, we conducted a mutation screening for SQSTM1 gene variants in 82 PDB patients and 100 control participants in Hungary. Mutations of SQSTM1 were detected in 18 PDB patients (21.95%); associations between genotype and clinical characteristics were also analyzed. Altogether, six different exonic alterations, including two types of UTR variants in the SQSTM1 gene, were observed in our PDB patients. Similarly, to previous genetic studies on Paget’s disease, our most commonly detected variant was the c.1175C > T (p.Pro392Leu) in nine cases (four in monostotic and five in polyostotic form). We have surveyed the germline SQSTM1 variant distribution among Hungarian patients with PDB. We also highlighted that the pattern of the analyzed disease-associated pathophysiological parameters could partially discriminate PDB patients with normal or mutant SQSTM1 genotype. However, our findings also underline and strengthen that not solely SQSTM1 stands in the background of the complex PDB etiology.

Genetic variation in the TNFRSF11A gene encoding RANK is associated with susceptibility to Paget's disease of bone

2010 ◽  
Vol 25 (12) ◽  
pp. 2592-2605 ◽  
Author(s):  
Pui Yan Jenny Chung ◽  
Greet Beyens ◽  
Philip L Riches ◽  
Liesbeth Van Wesenbeeck ◽  
Fenna de Freitas ◽  
...  
Keyword(s):  
Genetic Variation ◽  
Paget’S Disease ◽  
Paget's Disease ◽  
Paget’S Disease Of Bone ◽  
Paget's Disease Of Bone ◽  
Gene Encoding

Genetics of Paget's disease of bone

2005 ◽  
Vol 109 (3) ◽  
pp. 257-263 ◽  
Author(s):  
Anna Daroszewska ◽  
Stuart H. Ralston
Keyword(s):  
Paget’S Disease ◽  
Nuclear Factor Κb ◽  
Paget's Disease ◽  
Paget’S Disease Of Bone ◽  
Signalling Pathway ◽  
Common Disease ◽  
Paget's Disease Of Bone ◽  
Gene Encoding ◽  
Sequestosome 1 ◽  
Candidate Loci

PDB (Paget's disease of bone) is a common condition characterized by focal increases in bone turnover affecting one or more sites throughout the skeleton. Genetic factors are important in the pathogenesis of PDB and many families have been described where PDB is inherited in an autosomal-dominant fashion. Several candidate loci for susceptibility to PDB and related syndromes have been identified by genome-wide scans and recent evidence suggests that mutations in genes that encode components of the RANK [receptor activator of NF-κB (nuclear factor-κB)]/NF-κB signalling pathway play an important role in the pathogenesis of this group of diseases. Insertion mutations in the TNFRSF11A gene encoding RANK have been identified as the cause of familial expansile osteolysis, some cases of early onset PDB and expansile skeletal hyperphosphatasia. Inactivating mutations in the TNFRSF11B gene that encodes OPG (osteoprotegerin) have been found to cause the syndrome of juvenile PDB. Polymorphisms in OPG also appear to increase the risk of developing PDB. The most important causal gene for classical PDB is Sequestosome 1 (SQSTM1), which is a scaffold protein in the NF-κB signalling pathway, and mutations affecting the UBA (ubiquitin-associated) domain of this protein occur in between 20–50% of familial and 10–20% of sporadic PDB cases. The rare syndrome of IBMPFD (inclusion body myopathy, PDB and fronto-temporal dementia) is due to mutations in the VCP gene and these also cluster in the domain of VCP that interacts with ubiquitin, suggesting a common disease mechanism with SQSTM1-mediated PDB.

Paget's Disease of Bone

2006 ◽  
Vol 39 (11) ◽  
pp. 20
Author(s):  
Elizabeth Mechcatie ◽  
Lora T. McGlade
Keyword(s):  
Paget’S Disease ◽  
Paget's Disease ◽  
Paget’S Disease Of Bone ◽  
Paget's Disease Of Bone

Variants in RIN3 predispose to Paget's disease of bone

2014 ◽  
Author(s):  
Maheva Vallet ◽  
Antonia Sophocleous ◽  
Jon Warner ◽  
Stewart W Morris ◽  
James F Wilson ◽  
...  
Keyword(s):  
Paget’S Disease ◽  
Paget's Disease ◽  
Paget’S Disease Of Bone ◽  
Paget's Disease Of Bone
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