Age and origin of the G774A mutation in<i>SLC22A12</i>causing renal hypouricemia in Japanese

Ichida, Kimiyoshi; Hosoyamada, Makoto; Kamatani, Naoyuki; Kamitsuji, Shigeo; Hisatome, Ichiro; Shibasaki, Toshiaki; Hosoya, Tatsuo

doi:10.1111/j.1399-0004.2008.01021.x

Cited by 82 publications

(76 citation statements)

References 46 publications

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“…The population growth rate, d was set to 0.08 as previously described. 7 The allele, frequency of which was higher in the five chromosomes than that in the general population was regarded as the ancestral allele. We excluded the markers in the region less than 60 kb from the disease locus.…”

Section: Estimation Of the Mutation Agementioning

confidence: 99%

A founder mutation of CANT1 common in Korean and Japanese Desbuquois dysplasia

et al. 2011

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Desbuquois dysplasia (DBQD) is a severe skeletal dysplasia of autosomal recessive inheritance. DBQD is classified into types 1 and 2 based on presence or absence of hand anomalies. In a previous study, we found a CANT1 (for calcium-activated nucleotidase 1) mutation, c.676G4A in five DBQD families. They were all East Asians (Japanese or Korean). The high prevalence of the same mutation among Japanese and Korean suggested that it is a common founder mutation in the two populations. To examine a possible common founder, we examined the region around CANT1 in chromosomes with c.676G4A mutation by genotyping polymorphic markers in the region for the families. We examined their haplotypes using the family data. We identified in all families a common haplotype containing the CANT1 mutation that ranged up to 550 kb. The two unrelated carriers of the mutation in general populations in Korea and Japan could also have the haplotype. We estimated the age of the founder mutation as B1420 years (95% CI¼880-1940 years). The c.676G4A mutation of CANT1 commonly seen in Japanese and Korean DBQD should be derived from a common founder.

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Section: Estimation Of the Mutation Agementioning

confidence: 99%

A founder mutation of CANT1 common in Korean and Japanese Desbuquois dysplasia

et al. 2011

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“…5,6 Furthermore, renal excretion of UA in these patients is markedly higher: Fractional excretion of UA in all homozygous members was Ͼ150%, compared with 13% in those with heterozygous GLUT9 mutations and 40 to 90% in patients with homozygous loss of URAT1. 5,6,8 The human SLC2A9 gene, cloned in 2000, 20 encodes two isoforms of GLUT9 -long and short ( Figure 3A)-through the use of alternative promoters. In the kidney, GLUT9L is localized to the basolateral membrane of proximal tubular epithelial cells, whereas GLUT9S is localized to the apical membrane of these cells.…”

Section: Basic Research Wwwjasnorgmentioning

confidence: 99%

Homozygous SLC2A9 Mutations Cause Severe Renal Hypouricemia

Dinour¹,

Gray

Campbell

et al. 2010

Journal of the American Society of Nephrology

202

175

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Hereditary hypouricemia may result from mutations in the renal tubular uric acid transporter URAT1. Whether mutation of other uric acid transporters produces a similar phenotype is unknown. We studied two families who had severe hereditary hypouricemia and did not have a URAT1 defect. We performed a genome-wide homozygosity screen and linkage analysis and identified the candidate gene SLC2A9, which encodes the glucose transporter 9 (GLUT9). Both families had homozygous SLC2A9 mutations: A missense mutation (L75R) in six affected members of one family and a 36-kb deletion, resulting in a truncated protein, in the other. In vitro, the L75R mutation dramatically impaired transport of uric acid. The mean concentration of serum uric acid of seven homozygous individuals was 0.17 Ϯ 0.2 mg/dl, and all had a fractional excretion of uric acid Ͼ150%. Three individuals had nephrolithiasis, and three had a history of exercise-induced acute renal failure. In conclusion, homozygous loss-of-function mutations of GLUT9 cause a total defect of uric acid absorption, leading to severe renal hypouricemia complicated by nephrolithiasis and exercise-induced acute renal failure. In addition to clarifying renal handling of uric acid, our findings may provide a better understanding of the pathophysiology of acute renal failure, nephrolithiasis, hyperuricemia, and gout. 21: 64 -72, 201021: 64 -72, . doi: 10.1681 In most mammals, uric acid (UA) is oxidized by the hepatic enzyme uricase to highly soluble allantoin. In humans, however, this enzyme is inactive as a result of mutational silencing, 1 making UA the end product of purine metabolism. Serum UA concentration depends on both UA production and UA removal by the kidneys and intestinal tract and is high in humans compared with other mammals. Elevation of serum UA levels has been associated with various diseases, including gout, hypertension, and cardiovascular and renal disease. 2 Conversely, it has been suggested that UA has a beneficial role as a natural antioxidant, and low serum UA levels have been linked to several neurologic diseases. 2 Studies of renal handling of UA in humans have J Am Soc Nephrol

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“…220150, RHUC1). 3,[5][6][7][8] More than 10 patients with RHUC caused by heterozygous defects in the SLC2A9 gene, coding GLUT9, have been described in Japan (OMIM no. 612076, RHUC2).…”

Section: Introductionmentioning

confidence: 99%

“…Twenty-five mutations are disease causing. 3,[5][6][7][8][15][16][17][18][19] Five URAT1 variants have been described with a gout phenotype, 20 one variant is associated with increased FE-UA and two variants are associated with reduced FE-UA. 21,22 In this article we present clinical, biochemical, molecular genetics and functional characterization of previously reported p.R477H (CM042475 SNP, source HGMD-PUBLIC 2012.1) and novel p.G366R, p.L415_G417del and p.T467M variants in SLC22A12 gene responsible for RHUC1 in three Czech families.…”

Section: Introductionmentioning

confidence: 99%

Novel allelic variants and evidence for a prevalent mutation in URAT1 causing renal hypouricemia: biochemical, genetics and functional analysis

et al. 2013

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Renal hypouricemia (RHUC) is a heterogeneous inherited disorder characterized by impaired tubular uric acid (UA) transport with severe complications, such as acute kidney injury (AKI). Type 1 is caused by a loss-of-function mutation in the SLC22A12 gene (URAT1), type 2 in the SLC2A9 gene (GLUT9). This article describes three Czech families with RHUC type 1. The serum UA in the probands was 0.9, 1.1 and 0.5 mg/dl and expressed as an increase in the fractional excretion of UA (48, 43 and 39%). The sequencing analysis of SLC22A12 revealed three novel variants: p.G366R, p.T467M and a deletion p.L415_G417del. A detailed metabolic investigation in proband C for progressive visual failure supported suspicion of neuronal ceroid lipofuscinosis type 7 conditioned by the mutation in the MFSD8 gene. Functional studies showed significantly decreased urate uptake and a mis-localized URAT1 signal in p.G366R, p.L415_G417del and p.T467M. Furthermore, colocalization studies showed accumulation of URAT1 protein in the endoplasmic reticulum. The findings suggest that loss-of-function mutations cause RHUC via loss of UA absorption partly by protein misfolding. However, they do not necessarily lead to AKI and a possible genotype-phenotype correlation was not proposed. Furthermore, results confirm an uneven geographical and ethnic distribution of SLC22A12 variants; the p.L415_G417del mutation predominates in the Roma ethnic group in the Czech Republic.

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Age and origin of the G774A mutation inSLC22A12causing renal hypouricemia in Japanese

Cited by 82 publications

References 46 publications

A founder mutation of CANT1 common in Korean and Japanese Desbuquois dysplasia

A founder mutation of CANT1 common in Korean and Japanese Desbuquois dysplasia

Homozygous SLC2A9 Mutations Cause Severe Renal Hypouricemia

Novel allelic variants and evidence for a prevalent mutation in URAT1 causing renal hypouricemia: biochemical, genetics and functional analysis

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