惠州地区β缺失型地贫的基因诊断及临床特征分析
|
摘要
目的探讨惠州地区人群β缺失型地贫的检出率及临床特征,为基因诊断及产前诊断提供更好的指导。方法收集惠州市孕前、孕期检查夫妇19 585对,首先对血常规及血红蛋白电泳进行地贫筛查,对阳性者行基因诊断。对于疑为β地贫检出阴性者加用Gap-PCR技术检测β缺失型地贫。结果在364例样本中检出62例东南亚型HPFH(SEA-HPFH)、41例中国型~Gγ(~Aγδβ)~0和2例中国台湾型(Taiwanese),总检出率为0.27%。血常规结果显示β缺失型地贫携带者均表现为小细胞低色素,但贫血症状较轻或无贫血。血红蛋白电泳分析中SEA-HPFH和中国型~Gγ(~Aγδβ)~0缺失地贫携带者的血红蛋白F(HbF)明显增高,前者大部分的HbA_2升高而后者全部不增高。Taiwanese缺失地贫携带者HbA_2增高,但HbF没有明显增高。比较SEA-HPFH和中国型~Gγ(~Aγδβ)~0缺失杂合子的血液学特征,红细胞平均体积(MCV)、红细胞平均血红蛋白含量(MCH)、血红蛋白A(HbA)、血红蛋白A_2(HbA_2)和HbF的5组数据差异均有统计学意义(P<0.05)。结论惠州地区人群β缺失型地贫携带率高,呈现小细胞低色素特征,有明显的HbF升高。因此,应注意及重视β缺失型地贫的诊断,预防中、重型患儿的出生。
Objective To investigate the gene frequency and clinical features of β-thalassemia in Huizhou, so as to provide better guidance for genenetic and prenatal diagnosis. Methods A total of 19585 couples receiving pre-pregnancy and pregnancy examination in Huizhou were selected. Thalassemia screening was conducted by blood routine and hemoglobin electrophoresis, and further genetic diagnosis were conducted among the positive cases. The suspected β-thalassemia samples were processed by Gap-PCR. Results SEA-HPFH tpye, Chinese ~Gγ(~Aγδβ)~0 type and Taiwan type were revealed in 62, 41 and 2 cases among 364 samples, respectively. The total detection rate was 0.27%. The blood routine results of β-thalassemia carriers showed microcytic hypochromic anemia, but with mild or no symptoms of anemia. Hemoglobin analysis showed significant increase in HbF in SEA-HPFH and Chinese ~Gγ(~Aγδβ)~0 thalassemia carriers, in which HbA2 were increased in most of the former while not increased in the latter. Hb F was not significantly increased but only HbA2 increased in Taiwan type thalassemia carriers. Statistical differences were found in hematological phenotype indexes, including MCV, MCH, Hb A, Hb A2 and Hb F between the SEA-HPFH and Chinese ~Gγ(~Aγδβ)~0 heterozygous(P<0.05). Conclusion There is a high prevalence of β-thalassemia in Huizhou. Microcytic hypochromic anemia and increased HbF are common symptoms. Therefore, the prenatal diagnosis of β-thalassemia is critical to prevent the birth of children with moderate or severe disease.
Objective To investigate the gene frequency and clinical features of β-thalassemia in Huizhou, so as to provide better guidance for genenetic and prenatal diagnosis. Methods A total of 19585 couples receiving pre-pregnancy and pregnancy examination in Huizhou were selected. Thalassemia screening was conducted by blood routine and hemoglobin electrophoresis, and further genetic diagnosis were conducted among the positive cases. The suspected β-thalassemia samples were processed by Gap-PCR. Results SEA-HPFH tpye, Chinese ~Gγ(~Aγδβ)~0 type and Taiwan type were revealed in 62, 41 and 2 cases among 364 samples, respectively. The total detection rate was 0.27%. The blood routine results of β-thalassemia carriers showed microcytic hypochromic anemia, but with mild or no symptoms of anemia. Hemoglobin analysis showed significant increase in HbF in SEA-HPFH and Chinese ~Gγ(~Aγδβ)~0 thalassemia carriers, in which HbA2 were increased in most of the former while not increased in the latter. Hb F was not significantly increased but only HbA2 increased in Taiwan type thalassemia carriers. Statistical differences were found in hematological phenotype indexes, including MCV, MCH, Hb A, Hb A2 and Hb F between the SEA-HPFH and Chinese ~Gγ(~Aγδβ)~0 heterozygous(P<0.05). Conclusion There is a high prevalence of β-thalassemia in Huizhou. Microcytic hypochromic anemia and increased HbF are common symptoms. Therefore, the prenatal diagnosis of β-thalassemia is critical to prevent the birth of children with moderate or severe disease.
引文
[1] 丁燕玲, 黄际卫. 地中海贫血罕见突变的研究进展[J]. 中国优生与遗传杂志, 2016,2 (2):4-5.
[2] 王春芳, 韦传东, 雷茗, 等. Gγ+(Aγδβ)0地中海贫血复合β地中海贫血家系的表型与基因型分析的警示[J]. 中国儿童保健杂志,2015, 23(11):1191-1193.
[3] Cui J, Azimi M, Baysdorfer C, et al. Application of multiplex ligation-dependent probe amplification to screen for β-globin cluster deletions: detection of two novel deletions in a multi ethnic population[J]. Hemoglobin, 2013, 37(3):241-256.
[4] He S, Wei Y, Lin L, et al. The prevalence and molecular characterization of (δβ) 0 -thalassemia and hereditary persistence of fetal hemoglobin in the Chinese Zhuang population[J]. J Clin Lab Anal, 2018, 32(3): doi: 10.1002/jcla.22304. Epub 2017 Aug 1.
[5] Yin A, Li B, Luo M, et al. The Prevalence and Molecular Spectrum of a-and b-Globin Gene Mutations in 14,332 Families of Guangdong Province, China[J]. PLoS One, 2014, 9(2): e89855.
[6] 陈剑虹, 钟泽艳, 官志扬, 等. 33例中国型Gγ(Aγδβ)0地中海贫血病例的临床分析[J]. 分子诊断与治疗杂志, 2017, 9(6):396-400.
[7] 王继成, 秦丹卿, 骆明勇, 等. 中国型Gγ+(Aγδβ)0地中海贫血的基因诊断和临床特征分析[J]. 分子诊断与治疗杂志, 2016, 8(4):227-230.
[8] 逄婷, 郭仲辉, 黄俊杰, 等. 东南亚型HPFH的突变检测及临床特征分析[J]. 中国优生与遗传杂志, 2016, 8(12):24-26.
[9] 杜丽, 秦丹卿, 王继成, 等. 5个家系δβ地中海贫血的家系分析及产前诊断[J]. 分子诊断与治疗杂志, 2015, 7(1):27-32.
[10] 朱晓洁, 刘露, 刘瑞玉, 等. 一例罕见的缺失型β地中海贫血及其家系分析[J]. 中国热带医学杂志, 2017, 17(11):1154-1156.
[11] 钟泽艳, 陈剑虹, 贺海林, 等. 广东省惠州地区基于医院水平的地中海贫血基因突变谱分析[J]. 中国计划生育学杂志, 2015, 23(6):371-375.
[12] 杜丽, 秦丹卿, 兰菲菲, 等. 轻型β地中海贫血合并缺铁性贫血患者血红蛋白A_2水平的变化[J]. 广东医学, 2016, 37(13):1982-1984.
[13] Mondal SK, Mandal S. Prevalence of thalassemia and hemoglobinopathy in eastern India: A 10-year high-performance liquid chromatography study of 119,336 cases[J]. Asian J Transfus Sci, 2016, 10(1):105-110.
[14] 韦媛, 林丽, 陈碧艳, 等. 广西地区中国型Gγ(Aγδβ)0-地中海贫血的发病情况及表型特征[J]. 山东医药, 2016, 56(37):58-60.
[15] 杜若甫. 中国人群体遗传学[M]. 北京: 科学出版社, 2004:202-206.
[16] Fornari TA, Lanaro C, Albuquerque DM, et al. Modulation of fetal hemoglobin in hereditary persistence of fetal hemoglobin deletion type-2, compared to Sicilian δβ-thalassemia, by BCL11A and SOX6-targeting microRNAs[J]. Exp Biol Med(Maywood), 2017, 242(3):267-274.
[2] 王春芳, 韦传东, 雷茗, 等. Gγ+(Aγδβ)0地中海贫血复合β地中海贫血家系的表型与基因型分析的警示[J]. 中国儿童保健杂志,2015, 23(11):1191-1193.
[3] Cui J, Azimi M, Baysdorfer C, et al. Application of multiplex ligation-dependent probe amplification to screen for β-globin cluster deletions: detection of two novel deletions in a multi ethnic population[J]. Hemoglobin, 2013, 37(3):241-256.
[4] He S, Wei Y, Lin L, et al. The prevalence and molecular characterization of (δβ) 0 -thalassemia and hereditary persistence of fetal hemoglobin in the Chinese Zhuang population[J]. J Clin Lab Anal, 2018, 32(3): doi: 10.1002/jcla.22304. Epub 2017 Aug 1.
[5] Yin A, Li B, Luo M, et al. The Prevalence and Molecular Spectrum of a-and b-Globin Gene Mutations in 14,332 Families of Guangdong Province, China[J]. PLoS One, 2014, 9(2): e89855.
[6] 陈剑虹, 钟泽艳, 官志扬, 等. 33例中国型Gγ(Aγδβ)0地中海贫血病例的临床分析[J]. 分子诊断与治疗杂志, 2017, 9(6):396-400.
[7] 王继成, 秦丹卿, 骆明勇, 等. 中国型Gγ+(Aγδβ)0地中海贫血的基因诊断和临床特征分析[J]. 分子诊断与治疗杂志, 2016, 8(4):227-230.
[8] 逄婷, 郭仲辉, 黄俊杰, 等. 东南亚型HPFH的突变检测及临床特征分析[J]. 中国优生与遗传杂志, 2016, 8(12):24-26.
[9] 杜丽, 秦丹卿, 王继成, 等. 5个家系δβ地中海贫血的家系分析及产前诊断[J]. 分子诊断与治疗杂志, 2015, 7(1):27-32.
[10] 朱晓洁, 刘露, 刘瑞玉, 等. 一例罕见的缺失型β地中海贫血及其家系分析[J]. 中国热带医学杂志, 2017, 17(11):1154-1156.
[11] 钟泽艳, 陈剑虹, 贺海林, 等. 广东省惠州地区基于医院水平的地中海贫血基因突变谱分析[J]. 中国计划生育学杂志, 2015, 23(6):371-375.
[12] 杜丽, 秦丹卿, 兰菲菲, 等. 轻型β地中海贫血合并缺铁性贫血患者血红蛋白A_2水平的变化[J]. 广东医学, 2016, 37(13):1982-1984.
[13] Mondal SK, Mandal S. Prevalence of thalassemia and hemoglobinopathy in eastern India: A 10-year high-performance liquid chromatography study of 119,336 cases[J]. Asian J Transfus Sci, 2016, 10(1):105-110.
[14] 韦媛, 林丽, 陈碧艳, 等. 广西地区中国型Gγ(Aγδβ)0-地中海贫血的发病情况及表型特征[J]. 山东医药, 2016, 56(37):58-60.
[15] 杜若甫. 中国人群体遗传学[M]. 北京: 科学出版社, 2004:202-206.
[16] Fornari TA, Lanaro C, Albuquerque DM, et al. Modulation of fetal hemoglobin in hereditary persistence of fetal hemoglobin deletion type-2, compared to Sicilian δβ-thalassemia, by BCL11A and SOX6-targeting microRNAs[J]. Exp Biol Med(Maywood), 2017, 242(3):267-274.