Analysis of Genetic Diagnosis Results for Thalassemia in Childbearing Age Population in Baoshan Region
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摘要:
目的 了解云南省保山市育龄人群地中海贫血基因携带情况。 方法 利用高通量测序技术对874例样本进行α-地贫及β-地贫检测,统计分析人群分布特征。 结果 874例样本中检出地贫基因阳性样本251例,地贫基因的人群阳性率为28.72%(251/874);α-地贫基因阳性样本140例,阳性率为16.02%(140/874),以基因突变类型α α/-α3.7为主;β-地贫阳性样本95例,阳性率为10.87%(95/874),以基因型CD26为主;α β-复合型地贫基因阳性样本16例,阳性率为1.83%(16/874);汉族人群和少数民族人群地贫携带差异性比较差异具有统计学意义(P < 0.01)。此外另检出α-珠蛋白基因三联体阳性率为1.49%(13/874),以基因型α α αanti3.7为主。 结论 保山市是地贫高发地区,地中海贫血阳性率较高,最为常见的突变类型是α α/-α3.7和CD26。研究对保山地区地贫防控、临床遗传咨询工作提供了一定的理论依据。 -
关键词:
- 地中海贫血 /
- α-珠蛋白基因三联体 /
- 遗传咨询
Abstract:Objective To investigate the gene-carrying rate of thalassemia in the population of Baoshan. Methods A total of 874 samples were α-thalassemia and β-thalassemia detected by NGS, and the ethnic characteristics of the population were statistically analyzed. Results There were 251 cases of positive thalassemia gene, accounting for 28.72%(251/874). There were 140 α-thalassemia carriers, with a positive rate of 16.02% (140/874). The most common gene mutation type was α α/-α3.7. There were 95 β-thalassemia carriers, with a positive rate of 10.87% (95/874). The most common gene mutation type was CD26. There were 16 α- and β-thalassemia compound carriers, with a positive rate of 1.83% (16/874); Comparison of the differences between Han and Ethnic populations in thalassemia carry (P < 0.01) was statistically significant. There were 13 α-globin gene triplet carriers, with a positive rate of 1.49% (13/874). The most common gene mutation type was α α αanti3.7. Conclusion Baoshan region population has a high thalassemia carrier frequency. The most common gene mutation type was α α/-α3.7and CD26. This study provides theoretical support for thalassemia prevention and control as well as clinical genetic counseling in the Baoshan region. -
Key words:
- Thalassemia /
- α-globin gene triple /
- Genetic counseling
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表 1 α-地贫的基因突变类型
Table 1. Types of gene mutations in α-Thalassemia
基因型 n 构成比(%) αα/-α3.7 99 70.71 αα/--SEA 14 10.00 αα/αCSα 10 7.14 -α3.7/SEA 4 2.86 αα/-α4.2 4 2.86 αHKα/αα 2 0.43 -α/-α3.7 1 0.71 -α3.7/αCSα 1 0.71 -α3.7/--SEA 1 0.71 -α3.7/-α3.7 1 0.71 αα/αQSα(HBA2:c.377T>C) 1 0.71 Hb Hekinan II(HBA1:c.84G>T) 1 0.71 HBA1:c.293A>G 1 0.71 140 100 表 2 β-地贫的基因突变类型
Table 2. Types of gene mutations in β-Thalassemia
基因型 n 构成比(%) CD26(HBB:c.79G>A) 76 80 CD17(HBB:c.52A>T) 3 3.16 CD41-42(HBB:c.126_129delCTTT) 3 3.16 IVS-II-654(HBB:c.316-197C>T) 2 2.11 3,UTR+132(HBB:c.132C>T) 1 1.05 CD8/9(HBB:c.27dupG) 1 1.05 CD71-72(HBB:c.217dupA) 1 1.05 3,UTR+129(HBB:c.129T>A) 1 1.05 Hb G-Copenhagen(HBB:c.142G>A) 1 1.05 Hb New York(HBB:c.341T>A) 1 1.05 IVS-II-5(HBB:c.315+5G>C) 1 1.05 Hb Dhonburi(HBB:c.380T>G) 1 1.05 Hb GIbbon(HBB:c.373C>A) 1 1.05 αααanti3.7合并CD26 1 1.05 αααanti4.2合并CD26 1 1.05 95 100 表 3 少数民族地贫阳性携带情况
Table 3. Positive carrying of Thalassemia among ethnic minorities
少数民族 阳性人数(n) 人数(n) 阳性率(%) 构成比(%) 傣族 31 47 65.96 31.63 白族 21 57 36.84 21.43 彝族 16 48 33.33 16.33 傈僳族 9 42 21.43 9.18 景颇族 6 12 50 6.12 阿昌族 3 5 / 3.06 苗族 3 8 / 3.06 布依族 2 3 / 2.04 德昂族 2 4 / 2.04 满族 2 2 / 2.04 回族 1 4 / 1.02 水族 1 1 / 1.02 佤族 1 3 / 1.02 怒族 0 3 / 0 布朗族 0 3 / 0 纳西族 0 2 / 0 哈尼族 0 2 / 0 瑶族 0 1 / 0 壮族 0 1 / 0 总计 98 248 39.52 100 注:/少数民族5个阳性样本以内的不计算阳性率。 -
[1] Modell B,Darlison M. Global epidemiology of haemogobin disorders and derived service indicators[J]. Bull World Health Organ,2008,86(6):480-487. [2] 麦凤鸣,颜双鲤. 地中海贫血筛查指标的分析评价[J]. 中华全科医学,2013,11(03): 350+387. [3] 黄林环,王子莲. 地中海贫血的筛查[J]. 实用妇产科杂志,2023,39(02):87-90. [4] Rosatelli C,Falchi A,Scalas M,et al. Hematological48 phenotype of the double heterozygous state for alpha and beta thalassemia[J]. Hemoglobin.,1984,8(1):25-35. doi: 10.3109/03630268408996958 [5] Luo X,Zhang X M,Wu L S,et al. Prevalence and clinical phenotype of the triplicated α-globin genes and its ethnic and geographical distribution in Guizhou of China[J]. BMC Med Genomics.,2021,14(1):97. [6] He J,Song W H,Yang J L,et al. Next-generation sequencing improves thalassemia carrier screening among premarital adults in a high prevalence population: The Dai ethnic group,China[J]. Genetics in Medicine,2017,19(9):1022-1031. doi: 10.1038/gim.2016.218 [7] 江涛,吴波丹,黄丹,等. 云南省文山壮族苗族自治州地中海贫血筛查及基因诊断结果分析[J]. 昆明理工大学学报(自然科学版),2023,48(5):162-167. [8] Xu X M,Zhou Y Q,Luo G X,et al. The prevalence and spectrum of alpha and beta thalassaemia in Guangdong Province: Implications for the future health burden and population screening[J]. J Clin Pathol,2004,57(5):517-522. doi: 10.1136/jcp.2003.014456 [9] Xiong F,Sun M,Zhang X,et al. Molecular epidemiological survey of haemoglobinopathies in the Guangxi Zhuang Autonomous Region of Southern China[J]. Clin Genet,2010,78(2):139-148. doi: 10.1111/j.1399-0004.2010.01430.x [10] 王智慧,吴洁丽,白文静,等. 孕妇地中海贫血遗传性耳聋及脊髓性肌萎缩症三联筛查在出生缺陷预防中的作用[J]. 中国妇幼保健,2024,39(4):734-739. [11] 王芳,张汝益,邓东阳,等. 贵阳地区地中海贫血基因突变类型及民族分布特点分析[J]. 中国实验血液学杂志,2021,29(6):1887-1891. doi: 10.19746/j.cnki.issn1009-2137.2021.06.033 [12] Bancone G,Gilder Me,Chowwowat N,et al. Prevalences of inherited red blood cell disorders in pregnant women of different ethnicities living along the Thailand-Myanmar border[J]. Wellcome Open Res, 2017,2: 72. [13] Williams T N,Weatheralli D J. World Distribution,Population Genetics,and Health Burden of the Hemoglobinopathies[J]. Cold Spring Harbor Perspectives in Medicine,2012,2(9):1485-1495. [14] 杨锡彤,杨宗梅,马蓉,等. 云南省大理白族自治州地中海贫血基因诊断结果分析[J]. 中国全科医学,2019,22(35):4342-4345. [15] 姚莉琴,邹团标,刘锦桃,等. 云南省15个特有少数民族7岁以下儿童地中海贫血的调查研究[J]. 中华妇幼临床医学杂志(电子版),2013,9(3):337-343. doi: 10.3877/cma.j.issn.1673-5250.2013.03.013 [16] 滕聪聪,徐咏梅,唐树萍,等. 云南省德宏州傣族育龄人群地中海贫血流行病学调查[J]. 基础医学与临床,2022,42(10):1504-1508. [17] 唐健, 吕梦欣, 何建萍, 等. 昆明地区5284例孕妇地中海贫血基因检测分析[J]. 昆明医科大学学报,2020,41(7):80-84. [18] 朱宝生,贺静,张杰,等. 云南省地中海贫血基因携带者及患者α和β珠蛋白基因突变谱与产前基因诊断[J]. 中华妇产科杂志,2012,47(2):85-89. doi: 10.3760/cma.j.issn.0529-567x.2012.02.002 [19] 杨宇航. 基于高通量测序技术的贵州省地中海贫血分子流行病学特征分析[D]. 遵义: 遵义医学院,2019. [20] 魏小凤,徐湘民,郭晓玲等. 广东人群中α珠蛋白基因多拷贝频率分布研究[J]. 实用医学杂志,2020,36(10):1376-1380. doi: 10.3969/j.issn.1006-5725.2020.10.021 [21] Long J,Liu E. The carriage rates of α α αanti3.7,α α αanti4.2,and HKαα in the population of Guangxi,China measured using a rapid detection qPCR system to determine CNV in the α-globin gene cluster[J]. Gene,2021,768:145296. doi: 10.1016/j.gene.2020.145296 [22] Hamid M,Keikhaei B,Galehdari H,et al. Alpha-globin gene triplication and its effect in beta-thalassemia carrier,sickle cell trait,and healthy individual[J]. EJHaem,2021,2(3):366-374. [23] Nadkarni A,Phanasgaonkar S,Colah R,et al. Prevalence and molecular characterization of alpha-thalassemia syndromes among Indians[J]. Genet Test,2008,12(2):177-180. doi: 10.1089/gte.2007.0080 [24] Zhuang J,Jiang Y,Wang Y,et al. Molecular analysis of α-thalassemia and β-thalassemia in Quanzhou region Southeast China[J]. J Clin Pathol,2020,73(5):278-282. doi: 10.1136/jclinpath-2019-206179 [25] Quek L,Theins L. Molecular therapies in beta-thalassaemia[J]. Br J Haematol,2007,136(3):353-365. doi: 10.1111/j.1365-2141.2006.06408.x [26] Camaschella C,Mazza U,Roetto A,et al. Genetic interactions in thalassemia intermedia: analysis of beta-mutations,alpha-genotype,gamma-promoters,and beta-LCR hypersensitive sites 2 and 4 in Italian patients[J]. Am J Hematol,1995,48(2):82-87. doi: 10.1002/ajh.2830480203 [27] Premawardhena A,Fisher C A,Olivieri N F,et al. A novel molecular basis for beta thalassemia intermedia poses new questions about its pathophysiology[J]. Blood,2005,106(9):3251-3255. doi: 10.1182/blood-2005-02-0593 -