IR@PKUHSC  > 北京大学第二临床医学院  > 肾内科
学科主题临床医学
Abnormal expression and dysfunction of novel SGLT2 mutations identified in familial renal glucosuria patients
Yu, Lei; Lv, Ji-Cheng; Zhou, Xu-jie; Zhu, Li; Hou, Ping; Zhang, Hong
刊名HUMAN GENETICS
2011-03-01
DOI10.1007/s00439-010-0927-z
129期:3页:335-344
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 ; LOW-AFFINITY ; SLC5A2 ; CELLS
英文摘要

Familial renal glucosuria (FRG) is characterized by persistent glucosuria despite normal serum glucose and in the absence of overt tubular dysfunction. Mutation of sodium/glucose co-transporter 2 (SGLT2) has been identified and was recently reported to be involved in FRG. However, the functional and pathological consequences of such mutations remain unknown. In the current study, we collected four families with FRG. Sequencing of the SGLT2 coding region, intronic segments and cDNA revealed three missense mutations (294C > A: F98L; 1388T > G: L463R; 1435C > G: R479G) and two splice mutations (IVS 1-16 C > A: Del exon3; IVS 11 + 1 G > C: Del exon11). The probands were either heterozygous or compound heterozygous for SGLT2 mutations, and had glucosuria quantified at 6-27 g/day. Human 293 cells were transfected with the plasmid constructs to study the expression and function of SGLT2 mutants in vitro. Confocal microscopy using green fluorescent protein (GFP) revealed that the mutation results in a loss of punctate membrane pattern typical of the wild-type SGLT2 except in the 294C > A mutant. All mutants had significantly lower transport capacity in comparison to the wild-type control (26.49-71.48%). Renal biopsy in one consenting proband revealed significantly lower SGLT2 expression in the apical side of the proximal convoluted tubule in comparison to both healthy and disease controls (minimal change disease and diabetic nephropathy). The current study provides functional clues regarding the SGLT2 molecule from genotype to phenotype in FRG families.

语种英语
WOS记录号WOS:000287211200011
引用统计
被引频次:19[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/400002259/59770
专题北京大学第二临床医学院_肾内科
北京大学第一临床医学院_肾脏内科
作者单位Peking Univ, Div Renal, Hosp 1, Inst Nephrol,Key Lab Renal Dis,Minist Hlth China, Beijing 100034, Peoples R China
推荐引用方式
GB/T 7714
Yu, Lei,Lv, Ji-Cheng,Zhou, Xu-jie,et al. Abnormal expression and dysfunction of novel SGLT2 mutations identified in familial renal glucosuria patients[J]. HUMAN GENETICS,2011,129(3):335-344.
APA Yu, Lei,Lv, Ji-Cheng,Zhou, Xu-jie,Zhu, Li,Hou, Ping,&Zhang, Hong.(2011).Abnormal expression and dysfunction of novel SGLT2 mutations identified in familial renal glucosuria patients.HUMAN GENETICS,129(3),335-344.
MLA Yu, Lei,et al."Abnormal expression and dysfunction of novel SGLT2 mutations identified in familial renal glucosuria patients".HUMAN GENETICS 129.3(2011):335-344.
条目包含的文件
条目无相关文件。
个性服务
推荐该条目
保存到收藏夹
查看访问统计
导出为Endnote文件
谷歌学术
谷歌学术中相似的文章
[Yu, Lei]的文章
[Lv, Ji-Cheng]的文章
[Zhou, Xu-jie]的文章
百度学术
百度学术中相似的文章
[Yu, Lei]的文章
[Lv, Ji-Cheng]的文章
[Zhou, Xu-jie]的文章
必应学术
必应学术中相似的文章
[Yu, Lei]的文章
[Lv, Ji-Cheng]的文章
[Zhou, Xu-jie]的文章
相关权益政策
暂无数据
收藏/分享
所有评论 (0)
暂无评论
 

除非特别说明,本系统中所有内容都受版权保护,并保留所有权利。