title: Novel URAT1 mutations caused acute renal failure after exercise in two Chinese families with renal hypouricemia.
abstract: 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.
authors.affiliation: Department of Internal Medicine and Institute of Hypertension, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Zongzhe
authors.initials: Z
authors.lastname: Li
authors.forename: Hu
authors.initials: H
authors.lastname: Ding
authors.forename: Chen
authors.initials: C
authors.lastname: Chen
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.forename: Dao Wen
authors.initials: DW
authors.lastname: Wang
authors.forename: Yongman
authors.initials: Y
authors.lastname: Lv
mesh_terms: D058186:Acute Kidney Injury / Q000209:etiology* / Q000503:physiopathology; D000328:Adult; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D002681:China; D015444:Exercise; D005091:Exons; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D027361:Organic Anion Transporters / Q000235:genetics*; D027701:Organic Cation Transport Proteins / Q000235:genetics*; D010375:Pedigree; D015499:Renal Tubular Transport, Inborn Errors / Q000150:complications* / Q000235:genetics* / Q000503:physiopathology; D014545:Urinary Calculi / Q000150:complications* / Q000235:genetics* / Q000503:physiopathology; D055815:Young Adult
chemical_list: D027361:Organic Anion Transporters; D027701:Organic Cation Transport Proteins; C491241:SLC22A12 protein, human