Molecular analysis of the SGLT2 gene in patients with renal glucosuria
Molecular analysis of the SGLT2 gene in patients with renal glucosuria
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DOI：
10.1097/01.asn.0000092790.89332.d2
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发表时间：
2003-11-01
影响因子：
13.6
通讯作者：
Klaerke, D
中科院分区：
文献类型：
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作者：
Santer, R;Kinner, M;Klaerke, D
我们评估了SGLT2（肾钠依赖性葡萄糖转运蛋白基因）在肾性血糖中的作用。因此，对其基因组序列和内含子-外显子组织进行了测定，并对有索引病例的23个家族进行了突变分析。在21个家族中，检测到21种不同的SGLT2突变。其中大多数是私人的；在5个不同民族背景的家族中仅发现一个剪接突变，在2个德国家族中发现一个12bp的缺失。14例患者（包括最初的“肾型糖尿”患者）的SGLT2突变为纯合子或复合杂合子，导致血糖在14.6至202 g/1.73 m(2)/d （81 - 1120 mmol/1.73 m(2)/d）之间。他们的一些杂合家族成员的葡萄糖排泄量增加，最高可达4.4 g/1.73 m(2)/d （24 mmol/1.73 m(2)/d）。同样，在血糖低于10 g/1.73 m(2)/d （55 mmol/1.73 m(2)/d）的指标病例中，如果存在SGLT2突变，则总是在杂合状态下检测到。我们认为SGLT2在肾小管葡萄糖重吸收中起重要作用。肾性糖尿的遗传表现为外显率可变的共显性特征。
The role of SGLT2 (the gene for a renal sodium-dependent glucose transporter) in renal glucosuria was evaluated. Therefore, its genomic sequence and its intron-exon organization were determined, and 23 families with index cases were analyzed for mutations. In 21 families, 21 different SGLT2 mutations were detected. Most of them were private; only a splice mutation was found in 5 families of different ethnic backgrounds, and a 12-bp deletion was found in two German families. Fourteen individuals (including the original patient with 'renal glucosuria type 0') were homozygous or compound heterozygous for an SGLT2 mutation resulting in glucosuria in the range of 14.6 to 202 g/1.73 m(2)/d (81 - 1120 mmol/1.73 m(2)/d). Some, but not all, of their heterozygous family members had an increased glucose excretion of up to 4.4 g/1.73 m(2)/d (24 mmol/1.73 m(2)/d). Likewise, in index cases with glucosuria below 10 g/1.73 m(2)/d (55 mmol/1.73 m(2)/d) an SGLT2 mutation, if present, was always detected in the heterozygous state. We conclude that SGLT2 plays an important role in renal tubular glucose reabsorption. Inheritance of renal glucosuria shows characteristics of a codominant trait with variable penetrance.