@entity4261 ( @entity4261 ) is the second most common @entity2331 , after @entity170 . It is characterised by focal areas of increased and disorganised bone turnover, coupled with increased bone formation. This disease usually appears in the late stages of life, being slightly more frequent in @entity1 than in @entity1 . It has been reported worldwide, but primarily affects individuals of British descent. Majority of @entity4261 @entity1 are asymptomatic, but clinical manifestations include @entity158 , @entity79 , like pathological @entity174 and @entity2319 . The causes of the disease are poorly understood and it is considered as a complex trait, combining genetic predisposition with environmental factors. Linkage analysis identified @entity16402 , at chromosome 5q35, as directly related to the disease. A number of mutations in this gene have been reported, pP392L being the most common variant among different populations. Most of these variants affect the ubiquitin-associated (UBA) domain of the protein, which is involved in autophagy processes. Genome-wide association studies enlarged the number of loci associated with @entity4261 , and further fine-mapping studies, combined with functional analysis, identified @entity30626 and @entity69414 as causal genes for @entity4261 . A combination of risk alleles identified by genome-wide association studies led to the development of a score to predict disease severity, which could improve the management of the disease. Further studies need to be conducted to elucidate other important aspects of the trait, such as its focal nature and the epidemiological changes found in some populations. In this review, we summarize the clinical characteristics of the disease and the latest genetic advances to identify susceptibility genes. We also list current available treatments and prospective options.

Clinical and Genetic Advances in Paget's XXXX : a Review.

@entity1 :: ('9606', 'Species') :: ['women', 'patients', 'men'] @entity69414 :: ('79890', 'Gene') :: ['RIN3'] @entity174 :: ('MESH:D050723', 'Disease') :: ['fractures'] @entity16402 :: ('8878', 'Gene') :: ['SQSTM1'] @entity30626 :: ('10133', 'Gene') :: ['OPTN'] @entity170 :: ('MESH:D010024', 'Disease') :: ['osteoporosis'] @entity4261 :: ('MESH:D010001', 'Disease') :: ["Paget's disease of bone", "Paget's disease", 'PDB'] @entity2319 :: ('MESH:D003638', 'Disease') :: ['deafness'] @entity79 :: ('MESH:D001847', 'Disease') :: ['bone deformity and complications'] @entity2331 :: ('MESH:D001851', 'Disease') :: ['metabolic bone disorder'] @entity158 :: ('MESH:D010146', 'Disease') :: ['pain']
@entity79 :: (MESH:D001847,Disease) :: ['Disease of Bone']
