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Novel SLC5A2 Variants Contribute to Renal Glucosuria in Chinese Families: Abnormal Expression and Dysfunction of Variant SLC5A2
Yu, Lei1; Hou, Ping2; Lv, Ji-Cheng2; Liu, Guo-Ping1; Zhang, Hong2
关键词Familial Renal Glucosuria Slc5a2 Expression Function
刊名HUMAN MUTATION
2015
DOI10.1002/humu.22714
36期:1页:79-86
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Genetics & Heredity
研究领域[WOS]Genetics & Heredity
关键词[WOS]COTRANSPORTER SGLT2 ; MUTATION ; CELLS ; PATIENT ; GENE
英文摘要

Familial renal glucosuria (FRG) is characterized by persistent glucosuria despite normal serum glucose and the absence of overt tubular dysfunction. Variants in solute carrier family 5 (sodium-glucose cotransporter), member 2 (SLC5A2) have been reported in FRG patients. However, the functional and expression-related consequences of such variants have been scarcely investigated. In the current study, we studied five FRG families and identified six missense mutations, including four novel variants (c.1051T>C/.(C351R), c.1400T>C/p.(V467A), c.1420G>C/p.(A474P), c.1691G>A/p.(R564Q); RNA not analyzed) and two variants that had been previously reported (c.294C>A/p.(F98L), c.736C>T/p.(P246S); RNA not analyzed). The probands were either heterozygous or compound heterozygous for SLC5A2 variants and had glucosuria of 5.9%-19.6g/day. Human 293 cells were transfected with plasmid constructs to study the expression and function of SLC5A2 variants in vitro. Western blotting revealed that the expression levels of SLC5A2-351R-GFP, SLC5A2-467A-GFP, SLC5A2-474P-GFP, and SLC5A2-564Q-GFP were significantly decreased compared with wild-type SLC5A2-GFP (37%-55%). Confocal microscopy revealed that three variants (c.1400T>C, c.1420G>C, c.1691G>A) resulted in a loss of the punctate membrane pattern typical of wild-type SLC5A2. All variants had a significantly lower transport capacity in than the wild-type control. The current study provides a starting point to further investigate the molecular mechanism of SLC5A2 in FRG families and provides functional clues for antidiabetes drugs.

语种英语
WOS记录号WOS:000347076700012
项目编号81160087 ; 2010BS1102
资助机构National Natural Science Foundation of China ; Natural Science Fund of the Inner Mongolia Autonomous Region
引用统计
被引频次:5[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/52023
专题北京大学第一临床医学院_肾脏内科
作者单位1.Inner Mongolia Peoples Hosp, Div Renal, Hohhot 010017, Peoples R China
2.Peking Univ, Hosp 1, Inst Nephrol, Renal Div,Key Lab Renal Dis,Minist Hlth China, Beijing 100871, Peoples R China
推荐引用方式
GB/T 7714
Yu, Lei,Hou, Ping,Lv, Ji-Cheng,et al. Novel SLC5A2 Variants Contribute to Renal Glucosuria in Chinese Families: Abnormal Expression and Dysfunction of Variant SLC5A2[J]. HUMAN MUTATION,2015,36(1):79-86.
APA Yu, Lei,Hou, Ping,Lv, Ji-Cheng,Liu, Guo-Ping,&Zhang, Hong.(2015).Novel SLC5A2 Variants Contribute to Renal Glucosuria in Chinese Families: Abnormal Expression and Dysfunction of Variant SLC5A2.HUMAN MUTATION,36(1),79-86.
MLA Yu, Lei,et al."Novel SLC5A2 Variants Contribute to Renal Glucosuria in Chinese Families: Abnormal Expression and Dysfunction of Variant SLC5A2".HUMAN MUTATION 36.1(2015):79-86.
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