Novel URAT1 mutations caused acute renal failure after exercise in two Chinese families with renal hypouricemia

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• 作者：Zongzhe Li^a ; Hu Ding^a ; ^{huding@tjh.tjmu.edu.cn} ; Chen Chen^a ; Yan Chen^b ; Dao Wen Wang^a ; Yongman Lv^b ; ^{yongmanlu@yahoo.com.cn}
• 关键词：URAT1 or SLC22A12 ; Homo sapiens solute carrier family 22 member 12 gene ; GLUT9 or SLC2A9 ; Homo sapiens solute carrier family 2 member 9 gene ; RHUC ; renal hypouricemia ; RHUC1 ; renal hypouricemia type 1 ; RHUC2 ; renal hypouricemia type 2 ; EIARF ; exercise-ind
• 刊名：Gene
• 出版年：2013
• 出版时间：1 January, 2013
• 年：2013
• 卷：512
• 期：1
• 页码：97-101
• 全文大小：1364 K

文摘

Renal hypouricemia (RHUC), as an infrequent hereditary disease, is associated with severe complications such as exercise-induced acute renal failure (EIARF). Loss-of-function mutations in urate transporter gene URAT1 (Type 1) and in glucose transporter gene GLUT9 (Type 2) are major causes of this disorder. In this study, URAT1 and GLUT9 were screened in two uncorrelated families from mainland China and a total of five mutations were identified in exons, including two novel heterozygous URAT1 mutations. In four members of the first family, c.151delG (p.A51fsX64) in exon 1 was detected, which resulted in a frameshift and truncated the original 553-residue-protein to 63 amino acid protein. A missense mutation c.C1546A (p.P516T) in exon 9 in GLUT9 was revealed in the second family, which caused a functional protein substitution at codon 516. These two novel mutations were neither identified in the subsequent scanning of 200 ethnically matched healthy control subjects with normal serum UA level nor in a 1000 genome project database. Thus our report identifies two novel loss-of-function mutations (c.151delG in URAT1 and p.P516T in GLUT9) which cause RHUC and renal dysfunction in two independent RHUC pedigrees.