Original Article

Genetic variation analysis of neonatal hyperbilirubinemia: a single-center retrospective study

  • Qingyu LIU ,
  • Liwei WANG ,
  • Yilin LIN ,
  • Rui XIAO ,
  • Hui ZHOU ,
  • Xiaoqian ZHANG ,
  • Mengran FU ,
  • Hongying MI
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  • 1. Kunming University of Science and Technology, Kunming 650032, Yunnan, China
    2. Department of Neonatology, The First People's Hospital of Yunnan Province, Kunming 650032, Yunnan, China
    3. Kunming University of Science and Technology Affiliated Medical School, Kunming 650032, Yunnan, China

Received date: 2023-10-24

  Online published: 2024-09-04

Abstract

Objective To investigate the variation of genes related to neonatal hyperbilirubinemia jaundice and the diseases caused by hyperbilirubinemia jaundice, and its distribution in different degrees of jaundice. Methods A total of 167 neonates diagnosed with hyperbilirubinemia in NICU from July 2022 to July 2023 were selected and divided into severe and non-severe jaundice groups. Gene detection was performed by high-throughput second-generation gene sequencing technology. The jaundice gene variants were rated as pathogenicity, and the positive, carrying and negative rates of jaundice gene variants in children were analyzed, and the distribution of jaundice gene variation and related diseases in the two groups were also analyzed. Results Among 167 children, 18 cases (10.8%) were positive for jaundice gene variation, 55 cases (32.9%) were carriers, and 94 cases (56.3%) were negative. There were 8 genes involved in UGT1A1, ATP7B, HBB, SLC25A13, ATP8B1, SMPD1, G6PD and SLC10A1, among which the mutation frequency of UGT1A1 gene was up to 45.32%, and c.211G>A was the high frequency mutation site. In the group of 31 children with severe jaundice, 16 (51.6%) had positive results for jaundice gene mutations, and all 15 cases of Gilbert syndrome/Crigler-Najjar syndrome had UGT1A1 gene mutations. Among the 136 non-severe jaundice patients, only 2 cases (1.47%) were positive, and 1 case of Gilbert syndrome / Crigler-Najjar syndrome had a variation in UGT1A1 gene. Comparing the rates of positive, carrying and negative of jaundice gene variation between the two groups, the results showed that the positive rate of severe jaundice group was significantly higher than that of non-severe jaundice group, and the negative rate was significantly lower than that of non-severe jaundice group, with statistical significance (P<0.014). Conclusions Jaundice gene variation is closely related to the occurrence and severity of neonatal hyperbilirubinemia. The common cause is UGT1A1 gene variation, and c.211G>A is the high frequency mutation site. It is of great clinical significance to conduct gene detection for children with hyperbilirubinemia, especially severe hyperbilirubinemia.

Cite this article

Qingyu LIU , Liwei WANG , Yilin LIN , Rui XIAO , Hui ZHOU , Xiaoqian ZHANG , Mengran FU , Hongying MI . Genetic variation analysis of neonatal hyperbilirubinemia: a single-center retrospective study[J]. Journal of Clinical Pediatrics, 2024 , 42(9) : 782 -786 . DOI: 10.12372/jcp.2024.23e1015

References

[1] 邵肖梅, 叶鸿瑁, 丘小汕. 实用新生儿学[M]. 5版. 北京: 人民卫生出版社, 2019: 1150.
[2] 肖万祥, 杨婷, 张炼. 新生儿高胆红素血症再入院的现状和危险因素分析[J]. 中国当代儿科杂志, 2020, 22(9): 948-952.
[3] Wang X, Xiao T, Wang J, et al. Clinical and genetic risk factors associated with neonatal severe hyperbilirubinemia: a case-control study based on the China Neonatal Genomes Project[J]. Front Genet, 2024, 14: 1292921.
[4] 中华医学会儿科学分会新生儿学组, 《中华儿科杂志》编辑委员会. 新生儿高胆红素血症诊断和治疗专家共识[J]. 中华儿科杂志, 2014, 52(10): 745-748.
[5] 马素平. 高通量测序技术简述[J]. 科学与信息化, 2020(11): 137,140.
[6] 王秋菊, 沈亦平, 陈少科, 等. 遗传变异分类标准与指南[J]. 中国科学(生命科学), 2017, 47(6): 668-688.
[7] Li Y, Wu T, Chen L, et al. Associations between G6PD, OATP1B1 and BLVRA variants and susceptibility to neonatal hyperbilirubinaemia in a Chinese Han population[J]. J Paediatr Child Health, 2019, 55(9): 1077-1083.
[8] Boskabadi H, Rakhshanizadeh F, Zakerihamidi M. Evaluation of maternal risk factors in neonatal hyperbilirubinemia[J]. Arch Iran Med, 2020, 23(2): 128-140.
[9] Mehrad-Majd H, Haerian MS, Akhtari J, et al. Effects of Gly71Arg mutation in UGT1A1 gene on neonatal hyperbilirubinemia: a systematic review and meta-analysis[J]. J Matern Fetal Neonatal Med, 2019, 32(10): 1575-1585.
[10] 郝虎, 周伟, 石聪聪, 等. 基因筛查技术在新生儿常见遗传病筛查中的应用[J]. 中华实用儿科临床杂志, 2020, 35(22): 1712-1717.
[11] Rets A, Clayton AL, Christensen RD, et al. Molecular diagnostic update in hereditary hemolytic anemia and neonatal hyperbilirubinemia[J]. Int J Lab Hematol, 2019, 41 Suppl 1: 95-101.
[12] Nguyen TT, Zhao W, Yang X, et al. The relationship between hyperbilirubinemia and the promoter region and first exon of UGT1A1 gene polymorphisms in Vietnamese newborns[J]. Pediatr Res, 2020, 88(6): 940-944.
[13] Yang H, Wang Q, Zheng L, et al. Clinical significance of UGT1A1 genetic analysis in Chinese neonates with severe hyperbilirubinemia[J]. Pediatr Neonatol, 2016, 57(4): 310-317.
[14] Sood V, Lal BB, Sharma S, et al. Gilbert's syndrome in children with unconjugated hyperbilirubinemia - an analysis of 170 cases[J]. Indian J Pediatr, 2021, 88(2): 154-157.
[15] 尹迪, 魏珊珊, 许无恨, 等. UGT1A1基因多态性与新生儿不明原因重度高胆红素血症的关系[J]. 中华新生儿科杂志, 2021, 36(6): 55-58.
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