Suppr超能文献

儿童吉尔伯特综合征与基因研究结果:来自土耳其一家三级中心的经验

Gilbert Syndrome and Genetic Findings in Children: A Tertiary-Center Experience from Turkey.

作者信息

Çağan Appak Yeliz, Aksoy Betül, Özyılmaz Berk, Özdemir Taha Reşid, Baran Maşallah

机构信息

İzmir Katip Çelebi University, Departments of Pediatric Gastroenterology, Hepatology, and Nutrition, İzmir, Turkey.

SBU Tepecik Training and Research Hospital, Departments of Pediatric Gastroenterology, Hepatology, and Nutrition, İzmir, Turkey.

出版信息

Turk Arch Pediatr. 2022 May;57(3):295-299. doi: 10.5152/TurkArchPediatr.2022.21291.

Abstract

OBJECTIVE

Gilbert syndrome (GS) is a disease characterized by mildly elevated indirect serum bilirubin levels due to mutation in the promoter of the UGT1A1 gene, which causes a decrease in uridine diphosphate glucuronyltransferase enzyme activity. Gilbert syndrome should be considered based on clinical and laboratory findings in differential diagnosis, which can be supported by genetic analysis. This study aimed to evaluate the clinical findings and UGT1A1 mutations of children with Gilbert syndrome.

MATERIALS AND METHODS

Patients who were admitted to the pediatric gastroenterology clinic and who were considered to have Gilbert syndrome based on clinical and laboratory findings were included in the study. The UGT1A1 analysis was performed by Sanger sequence analysis.

RESULTS

A total of 56 children were included in the study. A(TA)7TAA, A(TA)6TAA, and (TA)6/7 allele promoter polymorphism was detected in 75.5%, 22.5%, and 2% of the patients, respectively. Other than these, in 3 patients, 3 different sequence variants associated with GS [c.880_893delinsA (p.Tyr294MetfsTer69) and c.1091C>T(p.Pro365Leu)] were detected.

CONCLUSION

We detected 7 TA repeats in the majority of our patients. A mild bilirubin elevation was determined in cases with 6 repetitions that were not considered risky for Gilbert syndrome. We concluded that the c.880_893delinsA (p.Tyr294MetfsTer69) variant, previously shown to be associated with Crigler-Najjar syndrome type I, may also be associated with partial enzyme deficiency leading to the Gilbert syndrome phenotype.

摘要

目的

吉尔伯特综合征(GS)是一种因尿苷二磷酸葡萄糖醛酸转移酶1A1(UGT1A1)基因启动子突变导致血清间接胆红素水平轻度升高的疾病,该突变会引起尿苷二磷酸葡萄糖醛酸转移酶活性降低。在鉴别诊断中,应根据临床和实验室检查结果考虑吉尔伯特综合征,基因分析可提供支持。本研究旨在评估吉尔伯特综合征患儿的临床特征及UGT1A1基因突变情况。

材料与方法

纳入儿科胃肠病门诊收治的、根据临床和实验室检查结果被认为患有吉尔伯特综合征的患者。采用桑格测序法进行UGT1A1分析。

结果

本研究共纳入56例患儿。分别在75.5%、22.5%和2%的患者中检测到A(TA)7TAA、A(TA)6TAA和(TA)6/7等位基因启动子多态性。除此之外,在3例患者中检测到与GS相关的3种不同序列变异[c.880_893delinsA(p.Tyr294MetfsTer69)和c.1091C>T(p.Pro365Leu)]。

结论

我们在大多数患者中检测到7个TA重复序列。在被认为对吉尔伯特综合征无风险的6次重复序列的病例中,确定有轻度胆红素升高。我们得出结论,先前显示与I型克里格勒 - 纳贾尔综合征相关的c.880_893delinsA(p.Tyr294MetfsTer69)变异,也可能与导致吉尔伯特综合征表型的部分酶缺乏有关。

相似文献

1
Gilbert Syndrome and Genetic Findings in Children: A Tertiary-Center Experience from Turkey.
Turk Arch Pediatr. 2022 May;57(3):295-299. doi: 10.5152/TurkArchPediatr.2022.21291.
2
Analysis of UGT1A1 genotype-phenotype correlation in Chinese patients with gilbert and crigler-Najjar II syndrome.
Eur J Med Genet. 2024 Oct;71:104962. doi: 10.1016/j.ejmg.2024.104962. Epub 2024 Jul 26.
4
UGT1A1 gene mutations in Pakistani children suffering from inherited nonhemolytic unconjugated hyperbilirubinemias.
Ann Hum Genet. 2013 Nov;77(6):482-7. doi: 10.1111/ahg.12039. Epub 2013 Aug 29.
5
Spectrum of UGT1A1 variants in Pakistani children affected with inherited unconjugated hyperbilirubinemias.
Clin Biochem. 2019 Jul;69:30-35. doi: 10.1016/j.clinbiochem.2019.05.012. Epub 2019 May 27.
8
[Gilbert disease and type I and II Crigler-Najjar syndrome due to mutations in the same UGT1A1 gene locus].
Med Klin (Munich). 2002 Sep 15;97(9):528-32. doi: 10.1007/s00063-002-1180-6.
10
Gilbert and Crigler Najjar syndromes: an update of the UDP-glucuronosyltransferase 1A1 (UGT1A1) gene mutation database.
Blood Cells Mol Dis. 2013 Apr;50(4):273-80. doi: 10.1016/j.bcmd.2013.01.003. Epub 2013 Feb 9.

本文引用的文献

1
(TA) Promoter Genotype: Diagnostic and Population Pharmacogenetic Marker in Serbia.
Balkan J Med Genet. 2018 Oct 29;21(1):59-68. doi: 10.2478/bjmg-2018-0012. eCollection 2018 Jun.
2
Genetic Variations and a Haplotype Associated with Neonatal Hyperbilirubinemia in Indonesian Population.
Biomed Res Int. 2018 Jan 23;2018:9425843. doi: 10.1155/2018/9425843. eCollection 2018.
3
Diagnostic criteria and contributors to Gilbert's syndrome.
Crit Rev Clin Lab Sci. 2018 Mar;55(2):129-139. doi: 10.1080/10408363.2018.1428526. Epub 2018 Feb 1.
4
Clinical Significance of UGT1A1 Genetic Analysis in Chinese Neonates with Severe Hyperbilirubinemia.
Pediatr Neonatol. 2016 Aug;57(4):310-7. doi: 10.1016/j.pedneo.2015.08.008. Epub 2015 Dec 2.
5
Inherited disorders of bilirubin clearance.
Pediatr Res. 2016 Mar;79(3):378-86. doi: 10.1038/pr.2015.247. Epub 2015 Nov 23.
8
Gilbert's syndrome.
BMJ. 2011 Apr 19;342:d2293. doi: 10.1136/bmj.d2293.
9
Hyperbilirubinemia syndromes (Gilbert-Meulengracht, Crigler-Najjar, Dubin-Johnson, and Rotor syndrome).
Best Pract Res Clin Gastroenterol. 2010 Oct;24(5):555-71. doi: 10.1016/j.bpg.2010.07.007.
10
The clinical application of UGT1A1 pharmacogenetic testing: gene-environment interactions.
Hum Genomics. 2010 Apr;4(4):238-49. doi: 10.1186/1479-7364-4-4-238.

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验