11例原发性肾性糖尿患儿SLC5A2基因变异分析

doi:10.12372/jcp.2022.22e0998

Abstract

Abstract:

Objective To summarize the clinical characteristics of children with primary renal glucosuria (PRG), and analyze the variation of SLC5A2 gene. Methods The clinical data and genetic test results of children diagnosed with PRG from 2013 to 2021 were retrospectively analyzed. Results There were 11 children (5 boys and 6 girls) with PRG, with a male/female ratio of 1:1.2. The median age at diagnosis was 29 months (1 day to 13 years). Five patients had a family history of glucosuria and none had a family history of diabetes. Two patients had mild and 9 patients had severe glucosuria. The blood glucose, glycated hemoglobin, insulin, C-peptide, renal function and renal ultrasound results were normal in all children. During the follow-up period, there were no symptoms of diabetes or systemic fatigue, and the children had normal growth and development without serious complications. No homozygous variation was found in SLC5A2 gene, the proportion of heterozygous variation was 36% (4/11), and the proportion of compound heterozygous variation was 64% (7/11). A total of 14 variants were found, including 10 missense variants, 1 deletion variant and 3 splicing variants. Among them, 5 variants have been reported in the literature, and 9 variants, p.S161F, p.A169T, p.P275L, p.A312P, p.A365T, p.Y410C, p.F471L, c. 1889_1891del, and c. 1665+5G> C, are new variants, which are predicted to be pathogenic by software and function. Among the 4 children with heterozygous variation, 2 had mild and 2 had severe glucosuria. Seven children with compound heterozygous variation showed severe diabetes. Conclusions SLC5A2 gene detection is helpful for the diagnosis of PRG. The clinical phenotype of PRG is correlated with its genotype. Heterozygous variation may show mild or severe glucosuria, while compound heterozygous variation mostly shows severe glucosuria. The clinical manifestation of children with PRG is mostly benign and does not affect the growth and development of children.

Key words: renal glucosuria, variation, genotype, phenotype

WAN Ling, CHEN Chaoying, TU Juan, LI Huarong. Analysis of SLC5A2 gene variation in 11 children with primary renal glucosuria[J].Journal of Clinical Pediatrics, 2022, 40(12): 912-918.

Figures/Tables 4

核苷酸改变	ACMG证据等级	ACMG
c.655G>A	PS4_Supporting：常染色体显性疾病，极罕见变异，在1个具有相同表型的无亲缘关系患者中观察到该变异。 PM2-supporting: 千人数据库、EXAC数据库中正常对照人群中未发现的变异。 PP3: 多种统计方法预测出该变异会对基因或基因产物造成有害的影响（REVEL:0.77）	VUS
c.1889_1891del	PM2-supporting: 千人数据库、EXAC数据库中正常对照人群中未发现的变异。 PM4_Supporting：非重复区框内插入/缺失或终止密码子丧失导致的蛋白质长度变化。	VUS
c.1540C>T	PS4_Moderate：常染色体显性疾病，极罕见变异，在最少3个具有相同表型的无亲缘关系患者中观察到该变异。 PM2-supporting: 千人数据库、EXAC数据库中低频变异。	VUS
IVS1-16C>A	PS4_Supporting：常染色体显性疾病，极罕见变异，在1个具有相同表型的无亲缘关系患者中观察到该变异。 PM2-supporting: 千人数据库、EXAC数据库中低频变异。	VUS
c.1229A>G	PM2-supporting: 千人数据库、EXAC数据库中正常对照人群中未发现的变异。 PP3: 多种统计方法预测出该变异会对基因或基因产物造成有害的影响（REVEL:0.83）	VUS
c.1665+5G>C	PM2-supporting: 千人数据库、EXAC数据库中低频变异。 PP3: 多种统计方法预测出该变异会对基因或基因产物造成有害的影响（Ada Score=1; RF Score=0.962）。	VUS
c.482C>T	PP3: 多种统计方法预测出该变异会对基因或基因产物造成有害的影响(REVEL=0.923)。	VUS
c.1449+1G>C	PM2-supporting: 千人数据库、EXAC数据库中正常对照人群中未发现的变异。 PP3: 多种统计方法预测出该变异会对基因或基因产物造成有害的影响（Ada Score=1; RF Score=0.932）。	VUS
c.505G>A	PM2-supporting: 千人数据库、EXAC数据库中低频变异。	VUS
c.736C>T	PM2-supporting: 千人数据库、EXAC数据库中低频变异。	VUS
c.1093G>A	PM2-supporting: 千人数据库、EXAC数据库中低频变异。 PP3: 多种统计方法预测出该变异会对基因或基因产物造成有害的影响(REVEL=0.889)。	VUS
c.824C>T	PM2-supporting: 千人数据库、EXAC数据库中正常对照人群中未发现的变异。 PP3: 多种统计方法预测出该变异会对基因或基因产物造成有害的影响(REVEL=0.815)。	VUS
c.1413C>	PM2-supporting: 千人数据库、EXAC数据库中低频变异。	VUS
c.934G>C	PM2-supporting: 千人数据库、EXAC数据库中低频变异。 PP3: 多种统计方法预测出该变异会对基因或基因产物造成有害的影响(REVEL=0.847)。	VUS

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病例编号	性别	发病年龄	家族史	起病表现	尿糖	核苷酸改变	氨基酸改变	Het/ Hom	父源/ 母源	是否报道	SIFT	Polyphen2	Mutation Taster
1	男	6岁	无	无	+++~++++	c.655G>A	p.A219T	Het	ND	Y	D	PD	D
2	男	13岁	无	无	+~++	c.1889_1891del	p.631del	Het	父源	N	NA	NA	NA
3	女	2岁5月	父尿糖+	外耳手术住院发现	+++~++++	c.1540C>T IVS1-16C>A	p.P514S 剪接变异	Het	母源父源	Y	T	PD	D
3	女	2岁5月	父尿糖+	外耳手术住院发现	+++~++++	c.1540C>T IVS1-16C>A	p.P514S 剪接变异	Het	母源父源	N	NA	NA	NA
4	男	2岁11月	父尿糖+	尿液黏稠	+++~++++	c.1229A>G c.1665+5G>C	p.Y410C 剪接变异	Het	父源母源	N	D	PD	D
4	男	2岁11月	父尿糖+	尿液黏稠	+++~++++	c.1229A>G c.1665+5G>C	p.Y410C 剪接变异	Het	父源母源	N	NA	NA	NA
5	女	1岁6月	父尿糖+	尿频	+++~++++	c.482C>T c.1449+1G>C	p.S161F 剪接变异	Het	父源母源	N	D	PD	D
5	女	1岁6月	父尿糖+	尿频	+++~++++	c.482C>T c.1449+1G>C	p.S161F 剪接变异	Het	父源母源	Y	NA	NA	NA
6	男	4岁	无	无	++++	c.505G>A IVS1-16C>A	p.A169T 剪接变异	Het	ND	N	T	PD	D
6	男	4岁	无	无	++++	c.505G>A IVS1-16C>A	p.A169T 剪接变异	Het	ND	Y	NA	NA	NA
7	女	2岁2月	无	尿色浑浊	++++	c.736C>T c.1093G>A	p.P246S p.A365T	Het	父源母源	Y	T	PD	D
7	女	2岁2月	无	尿色浑浊	++++	c.736C>T c.1093G>A	p.P246S p.A365T	Het	父源母源	N	D	PD	D
8	女	2岁	无	尿急	+++~++++	c.1449+1G>C	剪接变异	Het	母源	Y	NA	NA	NA
9	女	1岁7月	父尿糖+	无	+++~++++	c.824C>T c.1540C>T	p.P275L p.P514S	Het	父源母源	N	D	PD	D
9	女	1岁7月	父尿糖+	无	+++~++++	c.824C>T c.1540C>T	p.P275L p.P514S	Het	父源母源	Y	T	PD	D
10	女	1天	母尿糖+	黄疸住院发现	++++	c.1413C>G c.934G>C	p.F471L p.A312P	Het	父源母源	N	D	PD	D
10	女	1天	母尿糖+	黄疸住院发现	++++	c.1413C>G c.934G>C	p.F471L p.A312P	Het	父源母源	N	D	PD	D
11	男	7岁9月	无	无	+~++	c.505G>A	p.A169T	Het	母源	N	T	PD	D

Analysis of SLC5A2 gene variation in 11 children with primary renal glucosuria

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