关键词: SLC22A12 SLC2A9 glucose transporter 9 mutation rare disease renal hypouricemia urate transport 1 whole-exome sequence analysis

Mesh : Male Humans Exome Sequencing Uric Acid Renal Tubular Transport, Inborn Errors / genetics Computational Biology Rare Diseases Organic Anion Transporters / genetics Organic Cation Transport Proteins / genetics Glucose Transport Proteins, Facilitative / genetics

来  源:   DOI:10.3390/genes14091823   PDF(Pubmed)

Abstract:
Renal hypouricemia (RHUC) is a rare hereditary disorder caused by loss-of-function mutations in the SLC22A12 (RHUC type 1) or SLC2A9 (RHUC type 2) genes, encoding urate transporters URAT1 and GLUT9, respectively, that reabsorb urate in the renal proximal tubule. The characteristics of this disorder are low serum urate levels, high renal fractional excretion of urate, and occasional severe complications such as nephrolithiasis and exercise-induced acute renal failure. In this study, we report two Spanish (Caucasian) siblings and a Pakistani boy with clinical characteristics compatible with RHUC. Whole-exome sequencing (WES) analysis identified two homozygous variants: a novel pathogenic SLC22A12 variant, c.1523G>A; p.(S508N), in the two Caucasian siblings and a previously reported SLC2A9 variant, c.646G>A; p.(G216R), in the Pakistani boy. Our findings suggest that these two mutations cause RHUC through loss of urate reabsorption and extend the SLC22A12 mutation spectrum. In addition, this work further emphasizes the importance of WES analysis in clinical settings.
摘要:
肾高尿酸血症(RHUC)是一种罕见的遗传性疾病,由SLC22A12(RHUC1型)或SLC2A9(RHUC2型)基因的功能丧失突变引起,分别编码尿酸转运蛋白URAT1和GLUT9,重新吸收肾近曲小管中的尿酸盐。这种疾病的特点是血清尿酸水平低,高肾尿酸排泄分数,和偶尔的严重并发症,如肾结石和运动诱发的急性肾功能衰竭。在这项研究中,我们报道了两名西班牙(高加索人)兄弟姐妹和一名巴基斯坦男孩,他们的临床特征与RHUC相符.全外显子组测序(WES)分析确定了两个纯合变体:一种新的致病性SLC22A12变体,c.1523G>A;p.(S508N),在两个白人兄弟姐妹和先前报道的SLC2A9变体中,c.646G>A;p.(G216R),巴基斯坦男孩我们的发现表明,这两个突变通过尿酸盐重吸收的丧失引起RHUC,并扩展了SLC22A12突变谱。此外,这项工作进一步强调了临床环境中WES分析的重要性.
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