目的 分析中国9个家系家族性肾性糖尿（FRG）的致病基因SGLT2，测定先证者及其家族患病成员的肾葡萄糖阈，探讨FRG患者基因型与肾糖阈的相关性。 方法 PCR法扩增SGLT2全部编码区及其侧翼序列，用直接测序法分析 SGLT2 基因突变位点。检测 9个家系 FRG 先证者及其一级亲属共 25位家庭成员（其中21例患者）SGLT2 基因突变、24 h尿糖定量和肾葡萄糖阈（RTG）。比较不同基因型患者肾糖阈的差异。 结果 基因测序分析共发现12个SGLT2突变，其中未被人类基因突变数据库（HGMD）收录的新突变10 个，包括：c.331T＞C，p.W111R；c.374T＞C，p.M125T；c.394C＞T，p.R132C；c.612G＞C，p.Q204H；c.829C＞T，p.P277S；c.880G＞A，p.D294N；c.1129G＞A，p.G377S；c.1194C＞A，p.F398L；c.1540C＞T，p.P514S；c.1573C＞T，p.H525Y。中国人群特有的突变c.886（-10_-31）del等位基因突变频率高达28%（5/18）。复合杂合突变患者的RTG较杂合突变患者低[（1.28±0.10）mmol/L比（5.14±0.77）mmol/L，P＜0.001]；c.886（-10_-31）del携带者的RTG较其他杂合突变携带者低[（4.43±0.37）mmol/L比（5.70±0.51）mmol/L，P＜0.001]。 结论 发现10个新的突变基因型与中国人FRG相关，c.886（-10_-31）del可能为中国FRG人群的热点突变。复合杂合突变患者较杂合突变患者表现为更低的RTG。

Objective To analyze and identify the mutations in SGLT2 gene of nine Chinese families with FRG, and determine the renal threshold for glucose excretion (RTG), so as to explore the association of genotype and RTG. Methods All coding regions of SGLT2 gene, including intron exon boundaries, were analyzed using PCR followed by direct sequence analysis. Quantitative test for 24-hour urine glucose and RTG were measured among 9 probands (21 patients) and their family members from 9 pedigrees (total 25 subjects). The differences in renal glucose thresholds between patients with different genotypes (heterozygotes and compound heterozygotes; c.886(-10_-31) del heterozygotes and other heterozygotes) were compared. Results Twelve mutations were identified by SGLT2 gene analysis, including 10 novel ones that were not included in HGMD: c.331T＞C, p.W111R; c.374T＞C, p.M125T; c.394C＞T, p.R132C; c.612G＞C, p.Q204H; c.829C＞T, p.P277S; c.880G＞A, p.D294N; c.1129G＞A, p.G377S; c.1194C＞A, p.F398L; c.1540C＞T, p.P514S; c.1573C＞T, p.H525Y. In this study, the mutation c.886(-10_-31)del that is specific to Chinese population accounted for about 28% of the total alleles (5/18). The RTG values of patients with compound heterozygous mutations were much lower than those with simple heterozygous mutations [(1.28 ±0.10) vs (5.14±0.77) mmol/L; P＜0.001]; and c.886(-10_-31)del heterozygotes had significant lower RTG values than others [(4.43±0.37) vs (5.70±0.51) mmol/L, P＜0.001]. Conclusions Ten novel mutations which may be related to FRG are found in this study, and c.886(-10-31)del may be a hot-spot mutation in Chinese patients. Compound heterozygotes had much lower RTG values than simple heterozygotes.