影响β-地中海贫血表型的遗传修饰作用

doi:10.16288/j.yczz.19-131

遗传 ›› 2019, Vol. 41 ›› Issue (8): 669-676.doi: 10.16288/j.yczz.19-131

影响β-地中海贫血表型的遗传修饰作用

张倩倩,商璇,林宛颖,徐湘民()

南方医科大学基础医学院医学遗传学教研室,广州 510800

收稿日期:2019-05-13 修回日期:2019-07-29 出版日期:2019-08-20 发布日期:2019-08-05
通讯作者: 徐湘民 E-mail:xixm@smu.edu.cn
作者简介:张倩倩,博士研究生,专业方向：遗传学。E-mail: zqq.smu@foxmail.com
基金资助:
国家重点研发计划(2018YFA0507803);国家自然科学基金项目资助(81870148)

Effect of genetic modifiers on the clinical severity of β-thalassemia

Qianqian Zhang,Xuan Shang,Wanying Lin,Xiangmin Xu()

Department of Medical Genetics, Southern Medical University, Guangzhou 510800, China

Received:2019-05-13 Revised:2019-07-29 Online:2019-08-20 Published:2019-08-05
Contact: Xu Xiangmin E-mail:xixm@smu.edu.cn
Supported by:
Supported by the National Key Research and Development Program of China(2018YFA0507803);The National Natural Science Foundation of China(81870148)

摘要/Abstract

摘要：

β-地中海贫血(β-地贫)是一种可致死、致残的遗传性血液病,临床上具有较宽泛的表型变异谱,在致病基因型相同或类似的情况下,患者的临床表型严重程度有很大的差异。探索影响β-地贫表型的遗传修饰因素是当前血液病及遗传病领域的研究热点和重点。本文从α-珠蛋白基因型和胎儿血红蛋白(Hb F)数量性状位点两个方面阐述了可加重或缓解β-地贫表型的遗传修饰因素,并着重介绍了调控γ-珠蛋白基因重激活的转录因子变异,以及β-珠蛋白基因簇顺式元件变异。最后,本文举例介绍了β-地贫遗传修饰的临床应用以及未来发展前景。

关键词: β-地中海贫血, 胎儿血红蛋白, 遗传修饰作用, 基因编辑

Abstract:

β-thalassemia (β-thal) is a fatal and disabling inherited blood disorder with diverse phenotypes. The same or similar genotype of β-thal can manifest variable clinical severities. It is the hotspot and emphasis in the field of hematopathy and genetic diseases to explore genetic modifiers that influence the phenotype of β-thal. This review illustrates the deteriorating and amelioratig modifiers from two aspects: genotypes of α-globin and quantitative trait locus of fetal hemoglobin (Hb F). Variations of transcription factors which reactive the γ-globin gene expression and β-globin cluster cis-acting elements were introduced emphatically. Finally, clinical applications and future development prospects of β-thal genetic modifiers are introduced by examples.

Key words: β-thalassemia, fetal hemoglobin, genetic modifier effects, gene editing

张倩倩,商璇,林宛颖,徐湘民. 影响β-地中海贫血表型的遗传修饰作用[J]. 遗传, 2019, 41(8): 669-676.

Qianqian Zhang,Xuan Shang,Wanying Lin,Xiangmin Xu. Effect of genetic modifiers on the clinical severity of β-thalassemia[J]. Hereditas(Beijing), 2019, 41(8): 669-676.

参考文献

[1]	Taher AT, Weatherall DJ, Cappellini MD . Thalassaemia. Lancet, 2018,391(10116):155-167.
[2]	Xiangmin Xu. Guidelines for thalassemia prevention and control programme. People’s Military Medical Press, 2011.
[2]	徐湘民 . 地中海贫血预防控制操作指南. 北京:人民军医出版社, 2011
[3]	Cappellini MD, Cohen A, Porter J, Taher A, Viprakasit V, editors . Guidelines for the management of transfusion dependent thalassaemia (TDT) [Internet]. 3rd edition.Nicosia (CY): Thalassaemia International Federation; 2014.
[4]	Taher A, Vichinsky E, Musallam K, Cappellini MD Viprakasit V, authors Weatherall D, editor , Guidelines for the management of non transfusion dependent thalassaemia (NTDT) [Internet]. Nicosia,Cyprus: Thalassaemia International Federation; 2013.
[5]	Origa R . β-Thalassemia. Genet Med, 2017,19(6):609-619.
[6]	Shang X, Xu X . Update in the genetics of thalassemia: What clinicians need to know. Best Pract Res Cl Ob, 2017,9:3-15.
[7]	Mettananda S, Higgs DR . Molecular basis and genetic modifiers of thalassemia. Hematol Oncol Clin N, 2018,32(2):177-191.
[8]	Clark B, Shooter C, Smith F, Brawand D, Steedman L, Oakley M, Rushton P, Rooks H, Wang X, Drousiotou A, Kyrri A, Hadjigavriel M, Will A, Fisher C, Higgs DR, Phylipsen M, Harteveld C, Kleanthous M, Thein SL . Beta thalassaemia intermedia due to co-inheritance of three unique alpha globin cluster duplications characterised by next generation sequencing analysis. Br J Haematol, 2018,180(1):160-164.
[9]	Grandchamp B, Hetet G, Kannengiesser C, Oudin C, Beaumont C, Rodrigues-Ferreira S, Amson R, Telerman A, Nielsen P, Kohne E, Balser C, Heimpel H . A novel type of congenital hypochromic anemia associated with a nonsense mutation in the STEAP3/TSAP6 gene. Blood, 2011,118(25):6660-6666.
[10]	Liu D, Yi S, Zhang X, Fang P, Zheng C, Lin L, Cai R, Ye Y, Zhou Y, Liang Y, Cheng F, Zhang X, Zhou W, Mohandas N, An X, Xu X . Human STEAP3 mutations with no phenotypic red cell changes. Blood, 2016,127(8):1067-1071.
[11]	Ragab SM, Badr EA, Ibrahim AS . Evaluation of glutathione-S-Transferase P1 polymorphism and its relation to bone mineral density in egyptian children and adolescents with Beta-thalassemia Major. Mediterr J Hematol Infect Dis, 2016,8(1):e2016004.
[12]	Mokhtar GM, Sherif EM, Habeeb NM, Abdelmaksoud AA, El-Ghoroury EA, Ibrahim AS, Hamed EM . Glutathione S-transferase gene polymorphism: relation to cardiac iron overload in egyptian patients with beta thalassemia major. Hematology, 2015,21(1):46-53.
[13]	Mettananda S, Gibbons RJ, Higgs DR . α-Globin as a molecular target in the treatment of β-thalassemia.

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影响β-地中海贫血表型的遗传修饰作用

Effect of genetic modifiers on the clinical severity of β-thalassemia

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