Mutations in human urate transporter 1 gene in presecretory reabsorption defect type of familial renal hypouricemia.
To date, 11 loss of function mutations in the human urate transporter 1 (hURAT1) gene have been identified in subjects with idiopathic renal hypouricemia. In the present studies we investigated the clinical features and the mutations in the hURAT1 gene in seven families with presecretory reabsorption defect-type renal hypouricemia and in one family with the postsecretory reabsorption defect type. Twelve affected subjects and 26 family members were investigated. Mutations were analyzed by PCR and the direct sequencing method. Urate-transporting activities of wild-type and mutant hURAT1 were determined by [14C]urate uptake in Xenopus oocytes. Mutational analysis revealed three previously reported mutations (G774A, A1145T, and 1639-1643 del-GTCCT) and a novel mutation (T1253G) in families with the presecretory reabsorption defect type. Neither mutations in the coding region of hURAT1 gene nor significant segregation patterns of the hURAT1 locus were detected in the postsecretory reabsorption defect type. All hURAT1 mutants had significantly reduced urate-transporting activities compared with wild type (P < 0.05; n = 12), suggesting that T1253G is a loss of function mutation, and hURAT1 is responsible for the presecretory reabsorption defect-type familial renal hypouricemia. Future studies are needed to identify a responsible gene for the postsecretory reabsorption defect-type familial renal hypouricemia.
Wakida
Naoki
N
Department of Nephrology, Kumamoto University Graduate School of Medical Sciences, 1-1-1 Honjo, Kumamoto, Kumamoto 860-8556, Japan.
Tuyen
Do Gia
DG
Adachi
Masataka
M
Miyoshi
Taku
T
Nonoguchi
Hiroshi
H
Oka
Toshiaki
T
Ueda
Osamu
O
Tazawa
Masahiro
M
Kurihara
Satoshi
S
Yoneta
Yoshitaka
Y
Shimada
Hajime
H
Oda
Takashi
T
Kikuchi
Yuichi
Y
Matsuo
Hirotaka
H
Hosoyamada
Makoto
M
Endou
Hitoshi
H
Otagiri
Masaki
M
Tomita
Kimio
K
Kitamura
Kenichiro
K
D000293:Adolescent; D000328:Adult; D000368:Aged; D002352:Carrier Proteins / Q000235:genetics*; D002648:Child; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D009154:Mutation; D027361:Organic Anion Transporters / Q000235:genetics*; D027701:Organic Cation Transport Proteins; D015499:Renal Tubular Transport, Inborn Errors / Q000235:genetics*; D014527:Uric Acid / Q000378:metabolism*
D002352:Carrier Proteins; D027361:Organic Anion Transporters; D027701:Organic Cation Transport Proteins; C491241:SLC22A12 protein, human; D014527:Uric Acid