昆明地区357例Gilbert综合征基因变异谱分析

何建萍; 吕梦欣; 秦茂华; 朱丽虹; 党峰博; 孙永波; 罗胜军; 罗兰; 唐健

doi:10.12259/j.issn.2095-610X.S20231015

昆明地区357例Gilbert综合征基因变异谱分析

doi: 10.12259/j.issn.2095-610X.S20231015

1.
昆明市妇幼保健院医学遗传与产前诊断科，云南昆明　650031
2.
昆明医科大学基础医学院，云南昆明　650500

基金项目: 云南省科技厅科技计划基金资助项目（202101BA070001-252）；云南省生殖妇科疾病临床医学中心开放课题基金资助项目（2020LCZXKF-SZ19）；昆明市卫生科技人才培养项目“十百千”工程培养计划基金资助项目（2020-SW（后备）-98；昆明市卫生科技人才培养项目医学技术中心建设基金资助项目（2022-SW（技）-16）

详细信息

作者简介:
何建萍（1970～），女，云南昆明人，医学学士，副主任医师，主要从事产前筛查与诊断工作

通讯作者:
唐健，E-mail： 4556170233@qq.com

中图分类号: R394.3
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出版历程
- 收稿日期: 2023-05-29
- 刊出日期: 2023-10-25

Gene Variation Analysis of 357 Cases with Gilbert Syndrome in Kunming

1.
Dept. of Medical Genetics and Prenatal Diagnosis，Kunming Maternal and Child Health Hospital，Kunming Yunnan 650031
2.
School of Basic Medicine，Kunming Medical University，Kunming Yunnan 650041，China

摘要

摘要: 目的探讨昆明地区Gilbert综合征基因变异谱情况，为该疾病机制研究提供基础数据。方法应用高通量测序技术与生物信息学研究方法，对昆明地区357例Gilbert综合征患儿基因变异谱进行分析。结果在357例Gilbert综合征患儿中检出UGT1A1基因纯合变异82例，其中c.211G > A纯合变异占93.9%；c.1091C > T纯合变异占3.7%；c.1198A > C纯合变异占2.4%。检出 UGT1A1基因杂合变异275例，其中c.211G > A杂合变异占69.1%；c.1091C > T杂合变异占17.8%；c.1456T > G杂合变异占5.5%；c.1198A > C杂合变异占2.5%；c.1352C > T占1.1%；c.596C > G杂合变异占1.1%；c.1423C > T杂合变异占0.7%；c.1100G > A、c.1389G > C、c.610A > G、c.163C > T、c.715C > T、c.1021C > T杂合变异各占0.4%。结论昆明地区Gilbert综合征基因变异谱前3顺位为c.211G > A、c.1091C > T、c.1456T > G，与云南边境地区有所不同。为昆明地区非结合高胆红素血症疾病的诊断、预防及治疗提供了重要的参考依据，同时也为进一步探索非结合高胆红素血症的疾病发生机制提供了基础数据。
- Gilbert综合征 /
- 基因变异 /
- 高通量测序
Abstract: Objective To explore the gene variation profile of Gilbert syndrome in Kunming, and to provide basic data for the mechanisms of Gilbert syndrome. Methods 357 children with Gilbert syndrome in Kunming were analyzed by high-throughput sequencing and bio-information analysis. Results Among 357 children with Gilbert syndrome, 82 cases were found to have homozygous variations in the UGT1A1 gene, with c.211G > A homozygous variation accounting for 93.9% of the cases; c.1091C > T homozygous variation accounting for 3.7% of the cases; and c.1198A > C homozygous variation accounting for 2.4% of the cases. 275 cases were found to have heterozygous variations in the UGT1A1 gene, with c.211G > A heterozygous variation accounting for 69.1% of the cases; c.1091C > T heterozygous variation accounting for 17.8% of the cases;c.1456T > G heterozygous variation accounting for 5.5% of the cases; c.1198A > C heterozygous variation accounting for 2.5% of the cases; c.1352C > T accounting for 1.1% of the cases; c.596C > G heterozygous variation accounting for 1.1% of the cases; c.1423C > T heterozygous variation accounting for 0.7% of the cases; and c.1100G > A, c.1389G > C, c.610A > G, c.163C > T, c.715C > T, c.1021C > T heterozygous variations each accounting for 0.4% of the cases. Conclusion The top three gene variants associated with Gilbert's syndrome in the Kunming region were c.211G > A, c.1091C > T, c.1456T > G, which were different from those found in the border areas of Yunnan. This provides important reference data for the diagnosis, prevention, and treatment of unconjugated hyperbilirubinemia in the Kunming region, and also lays the foundation for further exploration of the pathogenesis of unconjugated hyperbilirubinemia.
- Gilbert syndrome /
- Genetic variation /
- High-throughput sequencing

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图 1 昆明地区357例Gilbert综合征基因变异位点测序图

A：c.211G > A纯合变异；B：c.1091C > T纯合变异；C：c.1198A > C纯合变异；D：c.211G > A杂合变异；E：c.1091C > T杂合变异；F：c.1456T > G杂合变异；G：c.1198A > C杂合变异；H：c.1352C > T杂合变异；I：c.596C > G杂合变异；J：c.1423C > T杂合变异；K：c.1100G > A杂合变异；L：c.1389G > C杂合变异；M：c.610A > G杂合变异；N：c.163C > T；O：c.715C > T杂合变异；P：c.1021C > T杂合变异。

Figure 1. 357 cases of Gilbert syndrome gene variant site sequencing diagram in Kunming

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表 1 昆明地区357例Gilbert综合征基因变异表

Table 1. Gene variation of 357 cases with Gilbert Syndrome in Kunming

基因	基因型	数量（n）	发生异常的染色体：碱基位置	致病性	核苷酸变化	氨基酸变化	数量（n）	占比（%）
UGT1A1	Hom	82	Chr2: 234669144	DFP	c.211G > A	p.Gly71Arg	77	93.9
			Chr2: 234676872	LP	c.1091C > T	p.Pro364Leu	3	3.7
			Chr2: 234676979	VUS	c.1198A > C	p.Asn400His	2	2.4
	Het	275	Chr2: 234669144	DFP	c.211G > A	p.Gly71Arg	190	69.1
			Chr2: 234676872	LP	c.1091C > T	p.Pro364Leu	49	17.8
			Chr2: 234681059	PAT	c.1456T > G	p.Tyr486Asp	15	5.5
			Chr2: 234676979	VUS	c.1198A > C	p.Asn400His	7	2.5
			Chr2: 234680955	VUS	c.1352C > T	p.Pro451Leu	3	1.1
			Chr2: 234669529	VUS	c.596C > G	p.Ser199Cys	3	1.1
			Chr2: 234681026	VUS	c.1423C > T	p.Arg475Cys	2	0.7
			Chr2: 234676881	VUS	c.1100G > A	p.Arg367His	1	0.4
			Chr2: 234680992^*	VUS	c.1389G > C	p.Glu463Asp	1	0.4
			Chr2: 234669543	VUS	c.610A > G	p.Met204Val	1	0.4
			Chr2: 234669096^*	VUS	c.163C > T	p.His55Tyr	1	0.4
			Chr2: 234669648	PAT	c.715C > T	p.Gln239Ter	1	0.4
			Chr2: 234676519	PAT	c.1021C > T	p.Arg341Ter	1	0.4
Hom：纯合变异；Het：杂合变异；PAT ：致病；LP：可能致病；VUS：意义不明；DFP：功能性多态，^*：该位点为 Clinvar与HGMD数据库未收录的变异位点。

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