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学科主题: 临床医学
题名:
Novel SLC5A2 Variants Contribute to Renal Glucosuria in Chinese Families: Abnormal Expression and Dysfunction of Variant SLC5A2
作者: 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
发表日期: 2015
DOI: 10.1002/humu.22714
卷: 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
所属项目编号: 81160087 ; 2010BS1102
项目资助者: National Natural Science Foundation of China ; Natural Science Fund of the Inner Mongolia Autonomous Region
WOS记录号: WOS:000347076700012
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/52023
Appears in Collections:北京大学第一临床医学院_肾脏内科_期刊论文

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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

Recommended Citation:
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.
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