Analysis of screening and genotypes of thalassemia in Liuzhou Area of Guangxi Province
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摘要: 目的 了解广西柳州地区地中海贫血(地贫)的筛查情况及基因类型的分布，为遗传咨询及防治措施提供科学依据。方法 以2016年1月至2020年12月就诊并进行筛查和基因检测的10 269例样本作为分析对象，通过血红蛋白电泳、血液学指标进行筛查，采用PCR结合反向斑点杂交和琼脂糖凝胶电泳方法及DNA测序技术进行地贫的基因类型及其构成比的分析。结果 β地贫筛查灵敏度明显高于α地贫的筛查灵敏度，差异有统计学意义(P< 0.05)。在α地贫基因携带者中，进行Hb电泳联合平均红细胞体积(MCV)、平均红细胞血红蛋白含量(MCH)筛查可明显提高筛查阳性率(P< 0.05)。10 269例就诊者中共检出4483例地贫基因携带者，阳性检出率43.66%，α地贫基因、β地贫基因和α复合β地贫基因的携带率分别为26.97%、14.49%和2.20%。26种α地贫基因类型中，以--SEA/αα、-α3.7/αα、αCSα/αα和-α4.2/αα为常见，其携带率分别为12.90%、4.10%、2.50%和1.71%，检出3例罕见α地贫；静止型α地贫、轻型α地贫和HbH所占比例分别为35.64%、50.96%和13.40%。32种β地贫基因类型，以β41-42/βN和β-17/βN为主，携带率分别为6.82%和4.52%，检出2种罕见型基因IVSⅡ-5和CD37。α复合β地贫基因型以β41-42/βN复合--SEA/αα和β41-42/βN复合-α3.7/αα为主。结论 Hb电泳联合MCV、MCH筛查可明显提高筛查阳性率。本地区地贫检出率较高，基因类型具有多样性，α地贫以--SEA/αα为主，β地贫以β41-42/βN为常见。本研究结果为制订地贫的筛查方案和开展优生工作提供参考数据。Abstract: Objective To investigate the screening and genotype in Yulin area to provide scientific basis for genetic consultation and prevention measures.Methods A total of 10 269 cases who underwent the thalassemia screening and gene detection in our hospital from Junuary 2016 to December 2020 wwere selected. The hemoglobin electrophoresis and hematology detection index were used to screening the thalassemia, and the polymerase reaction(PCR) combined with agargel eletrophoresis and reserve dot bolt hybridization was used to detect the types and constituent ratios of gene defects in thalassemia gene.Results The sensitivity of screening β-thalassemia was significantly higher than α-thalassemia, and combined application of hemoglobin electrophoresis and MCV and MCH could obviously improve the screening positive rate in α-thalassemia. A total of 4483 cases were identified as thalassemia gene detection or mutation in 10 269 cases with a detecting rate of 43.66%, and the detecting rate of α-thalassemia, β-thalassemia and α-combining β-thalassemia were 26.97%, 14.49% and 2.20% respectively. 26 kinds of α-thalassemia gene mutations were detected, the common mutations were as follows: --SEA/αα(12.90%), -α3.7/αα(4.10%),αCSα/αα(2.50%) and -α4.2/αα(1.71%), and including three rare gene mutations, the constituent ratio of Silent α-thalassemia, Minor α-thalassemia and HbH disease were 35.64%, 50.96% and 13.40% respectively. 32 kinds of β-thalassemia gene mutations were detected, the common mutations were as follows:β41-42/βN(6.82%) andβ-17/βN(4.52%), and including two rare gene mutations:IVSⅡ-5 andCD37. The main genotype of α-combining β-thalassemia wereβ41-42/βNcombining --SEA/ααandβ41-42/βNcombining -α3.7/αα.Conclusion Combined application of hemoglobin electrophoresis and MCV and MCH can obviously improve the screening positive rate of thalassemia. The detection rate of thalassemia gene was high in Liuzhou population, and there was diversity in mutation spectrums of thalassemia. The most common genotypes were --SEA/ααin α-thalassemia andβ41-42/βNin β-thalassemia. The results of this study can provide reference data for the scheme of screening, diagnosis and treatment of thalassemia and eugenics.
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Key words:
- thalassemia /
- screening /
- genotype /
- gene carring rate
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表 1 不同筛查方法的敏感性
例(%) 基因型 HbA2 MCV & MCH MCV & MCH & HbA2 静止型α地贫(753例) 380(50.46) 469(62.28) 608(80.74) 轻型α地贫(1018例) 765(75.15) 1012(99.41) 1017(99.90) 血红蛋白H病(199例) 189(94.97) 198(99.50) 199(100.00) α地贫(1970例) 1334(67.72) 1679(85.23) 1824(92.59) β地贫(1004例) 979(97.51) 993(98.90) 1004(100.00) 
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表 2 4483例地贫的分布
基因 例数 检出率/% 占比/% α地贫基因 2769 26.97 61.77 β地贫基因 1488 14.49 33.19 α复合β地贫基因 226 2.20 5.04 合计 4483 43.66 100.00
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表 3 2769例α地贫基因的分布
基因型 例数 携带率/% 占比/% -α3.7/αα 421 4.10 15.20 αCSα/αα 257 2.50 9.28 -α4.2/αα 176 1.71 6.36 αWSα/αα 95 0.93 3.43 αQSα/αα 37 0.36 1.34 HKαα/αα 1 0.01 0.04 --SEA/αα 1325 12.90 47.85 -α3.7/αCSα 15 0.15 0.54 αCSα/αCSα 14 0.14 0.51 -α3.7/-α3.7 11 0.11 0.40 -α3.7/-α4.2 8 0.08 0.29 -α3.7/αWSα 8 0.08 0.29 -α4.2/αCSα 6 0.06 0.22 -α4.2/αWSα 6 0.06 0.22 αCSα/αWSα 6 0.06 0.22 -α4.2/-α4.2 5 0.05 0.18 αCSα/αQSα 3 0.03 0.11 --THAI/αα 2 0.02 0.07 -α4.2/αQSα 1 0.01 0.04 -α3.7/αQSα 1 0.01 0.04 --SEA/αCSα 154 1.50 5.56 --SEA/-α3.7 139 1.35 5.02 --SEA/-α4.2 59 0.57 2.13 --SEA/αQSα 11 0.11 0.40 --SEA/αWSα 7 0.07 0.25 --THAI/αCSα 1 0.01 0.04
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表 4 148例β地贫基因的分布
基因型 例数 携带率/% 占比/% β41-42/βN 700 6.82 47.04 β-17/βN 464 4.52 31.18 β654/βN 83 0.81 5.58 β-28/βN 68 0.66 4.57 β71-72/βN 46 0.45 3.09 βE/βN 26 0.25 1.75 βIVSⅠ-1/βN 17 0.17 1.14 β43/βN 11 0.11 0.74 β27-28/βN 3 0.03 0.20 β-29/βN 2 0.02 0.13 β30/βN 1 0.01 0.07 β37/βN 1 0.01 0.07 β41-42/β41-42 11 0.11 0.74 β-17/β-17 7 0.07 0.47 β-28/β-28 2 0.02 0.13 βIVSⅡ-5/βIVSⅡ-5 1 0.01 0.07 β41-42/β-17 14 0.14 0.94 β41-42/β-28 6 0.06 0.40 β41-42/β654 4 0.04 0.27 β41-42/βE 4 0.04 0.27 β71-72/β654 3 0.03 0.20 β41-42/β71-72 2 0.02 0.13 β-17/β654 2 0.02 0.13 β-28/β654 2 0.02 0.13 β-17/β-28 1 0.01 0.07 β-17/β43 1 0.01 0.07 β-17/βIVSⅠ-1 1 0.01 0.07 β-17/βIVSⅡ-5 1 0.01 0.07 β41-42/β-29 1 0.01 0.07 β41-42/βIVSⅠ-1 1 0.01 0.07 β41-42/βIVSⅡ-5 1 0.01 0.07 βE/β43 1 0.01 0.07
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