A Recurrent Deletion in the SLC5A2 Gene Including the Intron 7 Branch Site Responsible for Familial Renal Glucosuria

Overview

Journal Sci Rep

Specialty Science

Date 2016 Sep 27

PMID 27666404

Citations 13

Authors

Xiangzhong Zhao

Li Cui

Yanhua Lang

Ting Liu

Jingru Lu

Cui Wang

Sylvie Tuffery-Giraud

Irene Bottillo

Xinsheng Wang

Leping Shao

Affiliations

Soon will be listed here.

Abstract

Familial renal glycosuria (FRG) is caused by mutations in the SLC5A2 gene, which codes for Na-glucose co-transporters 2 (SGLT2). The aim of this study was to analyze and identify the mutations in 16 patients from 8 families with FRG. All coding regions, including intron-exon boundaries, were analyzed using PCR followed by direct sequence analysis. Six mutations in SLC5A2 gene were identified, including five missense mutations (c.393G > C, p.K131N; c.1003A > G, p.S335G; c.1343A > G, p.Q448R; c.1420G > C, p.A474P; c.1739G > A, p.G580D) and a 22-bp deletion in intron 7 (c.886(-10_-31)del) removing the putative branch point sequence. By the minigene studies using the pSPL3 plasmids, we confirmed that the deletion c.886(-10_-31)del acts as a splicing mutation. Furthermore, we found that this deletion causes exclusion of exon 8 in the SCL5A2 transcript in patients. The mutation c.886(-10_-31)del was present in 5 (62.5%) of 8 families, and accounts for about 37.5% of the total alleles (6/16). In conclusion, six mutations resulting in FRG were found, and the c.886(-10_-31)del may be the high frequency mutation that can be screened in FRG patients with uniallelic or negative SLC5A2 mutations.

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