title: Clinical and functional characterization of URAT1 variants.
abstract: Idiopathic renal hypouricaemia is an inherited form of hypouricaemia, associated with abnormal renal handling of uric acid. There is excessive urinary wasting of uric acid resulting in hypouricaemia. Patients may be asymptomatic, but the persistent urinary abnormalities may manifest as renal stone disease, and hypouricaemia may manifest as exercise induced acute kidney injury. Here we have identified Macedonian and British patients with hypouricaemia, who presented with a variety of renal symptoms and signs including renal stone disease, hematuria, pyelonephritis and nephrocalcinosis. We have identified heterozygous missense mutations in SLC22A12 encoding the urate transporter protein URAT1 and correlate these genetic findings with functional characterization. Urate handling was determined using uptake experiments in HEK293 cells. This data highlights the importance of the URAT1 renal urate transporter in determining serum urate concentrations and the clinical phenotypes, including nephrolithiasis, that should prompt the clinician to suspect an inherited form of renal hypouricaemia.
authors.affiliation: Medical School, University Children's Hospital, Skopje, Macedonia.
authors.forename: Velibor
authors.initials: V
authors.lastname: Tasic
authors.forename: Ann Marie
authors.initials: AM
authors.lastname: Hynes
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Kitamura
authors.forename: Hae Il
authors.initials: HI
authors.lastname: Cheong
authors.forename: Vladimir J
authors.initials: VJ
authors.lastname: Lozanovski
authors.forename: Zoran
authors.initials: Z
authors.lastname: Gucev
authors.forename: Promsuk
authors.initials: P
authors.lastname: Jutabha
authors.forename: Naohiko
authors.initials: N
authors.lastname: Anzai
authors.forename: John A
authors.initials: JA
authors.lastname: Sayer
mesh_terms: D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D002648:Child; D019295:Computational Biology; D017124:Conserved Sequence / Q000235:genetics; D003710:Demography; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D027361:Organic Anion Transporters / Q000737:chemistry / Q000235:genetics*; D027701:Organic Cation Transport Proteins / Q000737:chemistry / Q000235:genetics*; D015499:Renal Tubular Transport, Inborn Errors / Q000235:genetics; D014545:Urinary Calculi / Q000235:genetics
chemical_list: D027361:Organic Anion Transporters; D027701:Organic Cation Transport Proteins; C491241:SLC22A12 protein, human