A recurrent deletion in the SLC5A2 gene including the intron 7 branch site responsible for familial renal glucosuria

作者：Zhao, Xiangzhong; Cui, Li; Lang, Yanhua; Liu, Ting; Lu, Jingru; Wang, Cui; Tuffery-Giraud, Sylvie; Bottillo, Irene; Wang, Xinsheng^*; Shao, Leping^*

来源：Scientific Reports, 2016, 6(1): 33920.

DOI：10.1038/srep33920

• SPLICING MUTATIONS
• SGLT2
• PATIENT

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.

• 出版日期2016-9-26
• 单位青岛大学