Identification of a novel variant within the 5'UTR of UMOD gene in a man with early-onset gout and chronic kidney disease

期刊連結：http://www.gouthyperuricemia.com Objective: To identify an early-onset gout subject with chronic kidney disease (CKD) of potential uromodulin (UMOD) genetic abnormality. Method: The subject’s UMOD genetic polymorphism was measured by PCR amplification of genomic DNA covering exons 3-12, and identified by restriction fragment length polymorphism (RFLP). Results: A functional mutation of G to A transition within the 5’UTR region of the UMOD gene at base –56 from the coding sequence was found. The new sequence of CCAT from CCGT within the 5’UTR creates a new binding site for transcription factor YY1. His urinary UMOD/creatinine (CRTN) ratio is 0.463mg/g, less than the UMOD/CRTN ratio (range 7-22mg/g) in other CKD patients with the same renal function. Given this, UMOD 5’UTR mutation is significantly associated with less urinary UMOD excretion and with a tendency to be associated with less estimated glomerular filtration rate (eGFR) in a small cohort study, we therefore postulated that this novel mutation causes decreased UMOD production and subsequent development of CKD. This novel disease phenotype is different from currently known UMOD storage disease which is characterized by production and deposition of aberrant UMOD protein in kidney tissue due to mutation in the coding sequence of UMOD gene. Conclusion: We suggest that in early-onset gout patients with CKD showing very low urinary UMOD excretion, not only coding sequence but also 5’UTR of UMOD gene should be carefully sequenced.