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学科主题: 临床医学
题名:
Abnormal expression and dysfunction of novel SGLT2 mutations identified in familial renal glucosuria patients
作者: Yu, Lei; Lv, Ji-Cheng; Zhou, Xu-jie; Zhu, Li; Hou, Ping; Zhang, Hong
刊名: HUMAN GENETICS
发表日期: 2011-03-01
DOI: 10.1007/s00439-010-0927-z
卷: 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
所属项目编号: 30825021 ; 30971371 ; 200800010086 ; 200802052
项目资助者: National Natural Science Foundation of China ; Specialized Research Fund for the Doctoral Program of Higher Education of China ; Foundation of Ministry of Health of China
WOS记录号: WOS:000287211200011
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/59770
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: Peking Univ, Div Renal, Hosp 1, Inst Nephrol,Key Lab Renal Dis,Minist Hlth China, Beijing 100034, Peoples R China

Recommended Citation:
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.
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