caa a22 4500 445861509 CHVBK 20180317145444.0 cr unu---uuuuu 170323e20110301xx s 000 0 eng 10.1007/s00439-010-0927-z doi (NATIONALLICENCE)springer-10.1007/s00439-010-0927-z Abnormal expression and dysfunction of novel SGLT2 mutations identified in familial renal glucosuria patients [Elektronische Daten] [Lei Yu, Ji-Cheng Lv, Xu-jie Zhou, Li Zhu, Ping Hou, Hong Zhang] 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 6-27g/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. Springer-Verlag, 2010 Yu Lei Renal Division, Peking University First Hospital, Peking University Institute of Nephrology, Key Laboratory of Renal Disease, Ministry of Health of China, 100034, Beijing, People's Republic of China aut Lv Ji-Cheng Renal Division, Peking University First Hospital, Peking University Institute of Nephrology, Key Laboratory of Renal Disease, Ministry of Health of China, 100034, Beijing, People's Republic of China aut Zhou Xu-jie Renal Division, Peking University First Hospital, Peking University Institute of Nephrology, Key Laboratory of Renal Disease, Ministry of Health of China, 100034, Beijing, People's Republic of China aut Zhu Li Renal Division, Peking University First Hospital, Peking University Institute of Nephrology, Key Laboratory of Renal Disease, Ministry of Health of China, 100034, Beijing, People's Republic of China aut Hou Ping Renal Division, Peking University First Hospital, Peking University Institute of Nephrology, Key Laboratory of Renal Disease, Ministry of Health of China, 100034, Beijing, People's Republic of China aut Zhang Hong Renal Division, Peking University First Hospital, Peking University Institute of Nephrology, Key Laboratory of Renal Disease, Ministry of Health of China, 100034, Beijing, People's Republic of China aut Human Genetics Springer-Verlag 129/3(2011-03-01), 335-344 0340-6717 129:3<335 2011 129 439 https://doi.org/10.1007/s00439-010-0927-z text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00439-010-0927-z text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Yu Lei Renal Division, Peking University First Hospital, Peking University Institute of Nephrology, Key Laboratory of Renal Disease, Ministry of Health of China, 100034, Beijing, People's Republic of China aut NATIONALLICENCE 700 1- Lv Ji-Cheng Renal Division, Peking University First Hospital, Peking University Institute of Nephrology, Key Laboratory of Renal Disease, Ministry of Health of China, 100034, Beijing, People's Republic of China aut NATIONALLICENCE 700 1- Zhou Xu-jie Renal Division, Peking University First Hospital, Peking University Institute of Nephrology, Key Laboratory of Renal Disease, Ministry of Health of China, 100034, Beijing, People's Republic of China aut NATIONALLICENCE 700 1- Zhu Li Renal Division, Peking University First Hospital, Peking University Institute of Nephrology, Key Laboratory of Renal Disease, Ministry of Health of China, 100034, Beijing, People's Republic of China aut NATIONALLICENCE 700 1- Hou Ping Renal Division, Peking University First Hospital, Peking University Institute of Nephrology, Key Laboratory of Renal Disease, Ministry of Health of China, 100034, Beijing, People's Republic of China aut NATIONALLICENCE 700 1- Zhang Hong Renal Division, Peking University First Hospital, Peking University Institute of Nephrology, Key Laboratory of Renal Disease, Ministry of Health of China, 100034, Beijing, People's Republic of China aut NATIONALLICENCE 773 0- Human Genetics Springer-Verlag 129/3(2011-03-01), 335-344 0340-6717 129:3<335 2011 129 439 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer