Novel homozygous insertion in SLC2A9 gene caused renal hypouricemia
Novel homozygous insertion in SLC2A9 gene caused renal hypouricemia
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DOI：
10.1016/j.ymgme.2010.12.016
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发表时间：
2011-04-01
影响因子：
3.8
通讯作者：
Sebesta, Ivan
中科院分区：
文献类型：
--
作者：
Stiburkova, Blanka;Ichida, Kimiyoshi;Sebesta, Ivan
肾性低尿酸血症是一种异质性遗传性疾病，其特征是肾小管中的尿酸处理功能受损。患者通常无症状;然而，有些患者可能会出现尿石症和/或急性肾损伤。大多数描述的患者（复合杂合子和/或纯合子）是SLC 22 A12基因突变的日本人（OMIM #220150）。最近报道了4例杂合缺陷引起的肾性低尿酸血症患者和2个SLC 2A 9基因纯合突变家族（OMIM #612076）。我们描述了一个捷克肾性低尿酸血症家族的临床病史、生化和分子遗传学结果。先证者（16岁的捷克女孩，父母不相关）的血清尿酸浓度为0.17 +/- 0.05 mg/dl，表示为尿酸排泄分数增加（194 +/- 99%）。对尿酸转运蛋白SLC 22 A12、SLC 2A 9、SLC 17 A3、ABCC 4和ABCG 2的编码区进行测序分析。基因组DNA分析显示，先证者及其兄弟的SLC 2A 9基因外显子3中存在一个新的核苷酸纯合子插入，导致蛋白质截短（p.Ile118HisfsX27）。在其他候选尿酸转运蛋白中没有发现序列变异。纯合子功能丧失突变通过尿酸吸收的完全丧失引起大量的肾性低尿酸血症;然而，它们不一定导致肾结石和急性肾损伤。与先前报道的2型肾性低尿酸血症杂合子患者相反，我们没有发现甚至轻微的低尿酸血症，也没有发现报告的兄弟姐妹的杂合子父母的FE-UA降低。(C)2010年爱思唯尔公司All rights reserved.
Renal hypouricemia is a heterogeneous inherited disorder characterized by impaired uric acid handling in the renal tubules. Patients are usually asymptomatic; however, some may experience urolithiasis and/or acute kidney injury. Most of the described patients (compound heterozygous and/or homozygous) are Japanese with mutations in the SLC22A12 gene (OMIM #220150). Four patients with renal hypouricemia caused by heterozygous defects and two families with homozygous mutations in the SLC2A9 gene have been recently described (OMIM #612076).We describe the clinical history, biochemical and molecular genetics findings of a Czech family with renal hypouricemia. The concentration of serum uric acid in the proband (16-year-old Czech girl with unrelated parents) was 0.17 +/- 0.05 mg/dl and expressed as an increase in the fractional excretion of uric acid (194 +/- 99%). The sequencing analysis of the coding region of uric acid transporters SLC22A12, SLC2A9, SLC17A3, ABCC4 and ABCG2, was performed. Analysis of genomic DNA revealed novel one nucleotide homozygote insertion in exon 3 in the SLC2A9 gene in proband and her brother resulting in a truncated protein (p. Ile118HisfsX27). No sequence variants in other candidate uric acid transporter were found. Homozygous loss-of-function mutations cause massive renal hypouricemia via total loss of uric acid absorption; however, they do not necessarily lead to nephrolithiasis and acute kidney injury. In contrast to previously reported heterozygous patients with renal hypouricemia type 2, we did not find even slight hypouricemia and found no decrease in the FE-UA of the heterozygous parents of the reported siblings. (C) 2010 Elsevier Inc. All rights reserved.