Gene Variation Analysis of 357 Cases with Gilbert Syndrome in Kunming
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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。 -
关键词:
- 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. -
Key words:
- 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
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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