title: Identification of a hypouricemia patient with SLC2A9 R380W, a pathogenic mutation for renal hypouricemia type 2.
abstract: Hypouricemia is characterized by low serum uric acid (SUA) levels (≤3.0 mg/dL) with complications such as urolithiasis and exercise-induced acute renal failure. We have previously reported that urate transporter 1 (URAT1/SLC22A12) and glucose transporter 9 (GLUT9/SLC2A9) are causative genes for renal hypouricemia type 1 (RHUC1) and renal hypouricemia type 2 (RHUC2), respectively. In the series of experiments, two families have been revealed to have RHUC2 due to GLUT9 missense mutations R198C or R380W, respectively. Thus far, however, no studies have reported other RHUC2 families or patients with these pathogenic mutations. This study is aimed to find other cases of RHUC2. We performed mutational analyses of GLUT9 exon 6 (for R198C) and exon 10 (for R380W) in 50 Japanese hypouricemia patients. Patients were analyzed out of a collection of more than 2000 samples from the Japan Multi-Institutional Collaborative Cohort Study (J-MICC Study). We identified a novel male patient with heterogeneous RHUC2 mutation R380W. The SUA of this hypouricemia patient was 2.6 mg/dL, which is similar to that of our previous report (SUA: 2.7 mg/dL). This is the second report indicating RHUC2 patient due to GLUT9 mutation R380W. This mutation occurs in highly conserved amino acid motifs and is reported to be an important membrane topology determinant. R380W is a dysfunctional mutation which completely diminishes the urate transport activities of GLUT9. Our study revealed a second hypouricemia patient with GLUT9 R380W, a pathogenic mutation of RHUC2, which may help to expand our understanding of RHUC pathogenesis.
authors.affiliation: a Department of Integrative Physiology and Bio-Nano Medicine , National Defense Medical College , Tokorozawa , Saitama , Japan.
authors.forename: Toshinori
authors.initials: T
authors.lastname: Chiba
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Matsuo
authors.forename: Shushi
authors.initials: S
authors.lastname: Nagamori
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Nakayama
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Kawamura
authors.forename: Seiko
authors.initials: S
authors.lastname: Shimizu
authors.forename: Masayuki
authors.initials: M
authors.lastname: Sakiyama
authors.forename: Makoto
authors.initials: M
authors.lastname: Hosoyamada
authors.forename: Sayo
authors.initials: S
authors.lastname: Kawai
authors.forename: Rieko
authors.initials: R
authors.lastname: Okada
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Hamajima
authors.forename: Yoshikatsu
authors.initials: Y
authors.lastname: Kanai
authors.forename: Nariyoshi
authors.initials: N
authors.lastname: Shinomiya
mesh_terms: D005260:Female; D051246:Glucose Transport Proteins, Facilitative / Q000737:chemistry / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D008297:Male; D008958:Models, Molecular; D009154:Mutation; D011487:Protein Conformation; D015499:Renal Tubular Transport, Inborn Errors / Q000175:diagnosis* / Q000235:genetics*
chemical_list: D051246:Glucose Transport Proteins, Facilitative; C411811:SLC2A9 protein, human
keywords: GLUT family; GLUT9L; GLUT9S; SLC transporters; renal urate reabsorption