Amplicon targeted resequencing for SLC2A9 and SLC22A12 identified novel mutations in hypouricemia subjects

Abstract

Background To identify potential causative mutations in SLC2A9 and SLC22A12 that lead to hypouricemia or hyperuricemia (HUA). Methods Targeted resequencing of whole exon regions of SLC2A9 and SLC22A12 was performed in three cohorts of 31 hypouricemia, 288 HUA and 280 normal controls. Results A total of 84 high‐quality variants were identified in these three cohorts. Eighteen variants were nonsynonymous or in splicing region, and then included in the following association analysis. For common variants, no significant effects on hypouricemia or HUA were identified. For rare variants, six single nucleotide variations (SNVs) p.T21I and p.G13D in SLC2A9 , p.W50fs, p.Q382L, p.V547L and p.E458K in SLC22A12, occurred in totally six hypouricemia subjects and were absent in HUA and normal controls. Allelic and genotypic frequency distributions of the six SNVs differed significantly between the hypouricemia and normal controls even after multiple testing correction, and p.G13D in SLC2A9 and p.V547L in SLC22A12 were newly reported. All these mutations had no significant effects on HUA susceptibility, while the gene‐based analyses substantiated the significant results on hypouricemia. Conclusion Our study first presents a comprehensive mutation spectrum of hypouricemia in a large Chinese cohort.

Renal hypouricemia complicated with kidney stone: a case report

“…Analyzing mutations through bioinformatics might help explain the related causes of RHUC ( 13 ). Previous experiments showed that changing one amino acid to p.R90H significantly lowers URAT1’s ability to transport uric acid, but it does not affect how it is produced or where it is located in the cell membrane ( 14 ).…”

Genetic Basis of the Epidemiological Features and Clinical Significance of Renal Hypouricemia

“…Among Roma populations and in Korea, where the same URAT1 mutant alleles were repeatedly identified, lower frequencies of GLUT9 mutant alleles than of URAT1 mutant alleles were reported [ 24 , 25 , 26 ]. In China, screening of the URAT1 and GLUT9 genes for mutations was performed in 31 individuals with hypouricemia (SUA concentration ≤2.0 mg/dL) selected from the general population [ 27 ], and this showed that the number of people with GLUT9 mutations was lower than that of people with URAT1 mutations (two vs. four, no mutations in the URAT1 or GLUT9 genes were found in the other 25 individuals). In this study, neither the URAT1 W258X nor R90H mutant alleles, which are the predominant genetic causes of renal hypouricemia in Japan and Korea, were identified.…”