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1,2 Hyperuricemia can lead to deposition of monosodium urate crystals in musculoskeletal structures, kidneys, and other tissues causing chronic inflammation, acute gout flares, and potentially chronic arthritis with joint damage and disfiguring tophi, kidney stones, and chronic kidney disease

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Taken together, it is reasonable to hypothesize that missense mutations on these residues can lead to severe clinical manifestations