目的 对2例罕见地中海贫血(地贫)家系进行分析及产前诊断。方法 采集家系成员外周血进行血细胞分析及毛细管电泳血红蛋白分析;采集外周血及羊水,用导流杂交法进行常规α和β地中海贫血基因检测;采用多重链接探针扩增技术(MLPA)、DNA测序、缺口PCR(Gap-PCR)技术及血红蛋白持续增多症缺失型电泳等技术分析其罕见基因型。结果 在2个家系中检测到1例罕见的越南型缺失β地中海贫血及1例东南亚缺失型α地贫复合α2基因CD124点突变;并对2个家系进行了产前诊断,检测到1个胎儿为越南型缺失β地中海贫血,另一个为东南亚缺失型α地贫。结论 当血液学表型与基因型不符时,应进一步做罕见基因型的检测以避免漏诊或误诊,特别是生育过重型地贫患儿的夫妇。这有助于指导临床诊断、人群筛查和遗传咨询。
Abstract
Objective To analyze 2 families with rare thalassemia and make prenatal diagnosis thalassemia. Methods The family members' peripheral blood samples were analyzed by whole blood cell analysis and hemoglobin analysis with capillary zone electrophoresis.Conventional α and β thalassemia genes were detected by flow-through hybridization for peripheral blood samples and amniotic fluid samples.Multi-Link Probe Amplification Technology(MLPA),DNA sequencing,gap PCR (Gap-PCR) and continuous electrophoresis of hemoglobin were used to analyze the rare genotypes. Results A case of rare type of β-thalassemia with Vietnamese deletion and a case of sea deletion compound of α2 gene CD124 mutation were detected in 2 families.To prenatal diagnosis among 2 families,one of the fetuses was detected for β-thalassemia with Vietnamese deletion,another was α thalassemia with sea deletion. Conclusions When the Results of hematological phenotype and genotype do not match,much attention should be paid to further detection of rare genotypes to avoid missed diagnosis or misdiagnosis,especially to the couples who have had children with severe thalassemia.The finding may enrich knowledge of the screening in thalassemia as well as the genetic counseling and clinical diagnosis.
关键词
罕见基因型 /
地中海贫血 /
产前诊断
Key words
rare genotype /
thalassemia /
prenatal diagnosis
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参考文献
[1] So CC,So AC,Chan AY,et al.Detection and characterization of beta-globin gene cluster deletions in Chinese using multi- plex ligation-dependent probe amplification[J].J Clin Pathol,2009,62(12):1107-1111.
[2] 卓永光,颜善活.钦州地区地中海贫血罕见基因型检出情况分析[J].内科杂志,2014,9(4):429-480.
[3] 黄海龙,郭丹华,林娜,等.两种中国人罕见β地中海贫血基因突变分析[J].中华检验医学杂志,2013,36(10):939-941.
[4] 刘兴梅,苏莉,李贵芳,等.贵州地区β-地中海贫血基因突变类型分析[J].中华医学遗传杂志,2014,31(5):561-563.
[5] 张强,范歆,何升,等.广西壮族自治区β地中海贫血基因突变分析[J].中华地方病学杂志,2014,33(6):615-618.
[6] 吕荣钰,飞球,陈小文,等.常规基因检测阴性的地中海贫血疑似病例再行进一步基因检测仍有7%的阳性发现[J].中国循证儿科杂志,2014,9(4):274-277.
[7] 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.
[9] 黄海龙,方颖迪,林娜,等.4种罕见β-地中海贫血基因检测膜条的制备及其临床应用[J].中国妇幼保健杂志,2016,31(1):127-129.
[8] 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.
[9] 谭梅,卢森,吴柳松,等.高通量测序技术在新生儿地中海贫血基因筛查中的应用[J].中国实验血液学杂志,2015,23(5):1404-1409.
[10] 钟良英,谢英俊,陈培松,等.广东地区汉族产前人群δ地贫基因的突变谱与血液学分析[J].中华医学杂志,2017:97(20):1580-1583.
[11] 颜善活,劳可干,符可鹏,等.一种罕见α-地贫基因突变HbH病(--SEA/α*92A>Gα)的家系分析与基因诊断[J].南方医科大学学报,2016,36(9):1295-1298.
[12] 黎永鉴,闫丽琼,陈唯.梧州市1365对地中海贫血筛查双阳夫妇泰国缺失型α地中海贫血基因诊断及产前诊断结果分析[J].吉林医学杂志,2017:38(2):317-319.
[13] 朱晓洁,刘宇鹏,刘瑞玉,等.惠州市同型α地中海贫血夫妇的胎儿产前地贫基因诊断分析[J].中国儿童保健杂志,2015,23(1):15-17.
[14] 杜丽,王继成,秦丹卿,等.泰国缺失型α 地中海贫血的家系分析及产前诊断[J].中国产前诊断杂志,2015,7(4):31-34.
基金
2017惠州市医疗卫生科技计划项目(2017Y009)
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