摘要
目的:探讨高通量测序技术(NGS)在产前筛查地中海贫血基因携带者的应用价值。方法:随机选取2018年11月至2019年1月在深圳市第二人民医院产科门诊产检的1036例孕妇,所有孕妇均进行血常规、血红蛋白电泳筛查,对血常规、血红蛋白电泳筛查阳性的孕妇进一步行常规地中海贫血基因检测[裂隙聚合酶链反应(Gap-PCR)技术结合膜反向斑点杂交(RBD)技术],同时对全部1036例孕妇进行NGS地中海贫血基因检测,了解地中海贫血基因在深圳地区孕妇群体中的携带情况,比较不同筛查模式下地中海贫血基因携带者的筛查效果及NGS的额外检出情况。结果:(1)所入组的孕妇群体中,地中海贫血基因总体携带率为8.98%,其中α地中海贫血携带率为7.05%,β地中海贫血携带率为1.54%,α合并β地中海贫血携带率为0.39%。人群中共检出15种地中海贫血基因型别,包括1例基因型为Hb Phnom Penh(HBA1:c.354_355insATC)的α地中海贫血和2例基因型为-50(G>A)的β地中海贫血。(2)不同血液学指标筛查地中海贫血的模式中,血常规、血红蛋白电泳联合筛查的灵敏度最高,但仍存在至少12.50%的漏诊率,且同时产生大量假阳性。(3)在本研究人群中,NGS与传统三级筛查结果完全一致,并且相比常规地中海贫血基因检测可额外检出3例非常见型别和4例意义不明的罕见β珠蛋白基因点突变。结论:NGS一次性筛查在产前阶段可显著降低地中海贫血基因携带者的漏诊率,并可额外检出罕见型别和未知基因变异。
Objective To explore the application value of using next-generation sequencing technology(NGS)to screen the thalassemia in pregnant women.Methods A total of 1036 pregnant women were randomly selected from the obstetrics clinic of Shenzhen Second People's Hospital from November 2018 to January 2019.All pregnant women underwent blood routine and hemoglobin electrophoresis screening.Pregnant women with positive blood routine and hemoglobin electrophoresis screening were further subjected to routine thalassemia gene detection[Gap polymerase chain reaction(GAP-PCR)technology combined with membrane reverse dot hybridization(RBD)technology],and NGS thalassemia gene detection was performed in all 1036 pregnant women.To investigate the carrying status of thalassemia gene in pregnant women in Shenzhen area,and compare the screening effect of thalassemia gene carriers and the additional detection of NGS under different screening modes.Results(1)The overall carrying rate of thalassemia gene was 8.98%in pregnant women,among which the carrying rate ofα-thalassemia was 7.05%.β-thalassemia was 1.54%.and the carrying rate ofα-thalassemia combinedβ-thalassemia was 0.39%.A total of 15 thalassemia genotypes were detected in the population,including 1 case of alpha thalassemia with Hb Phnom Penh(HBA1:c.354_355insATC)and 2 cases of beta thalassemia with-50(G>A).(2)Among the modes of screening thalassemia with different hematological indicators,the combined screening of routine blood and hemoglobin electrophoresis had the highest sensitivity,but there was still at least 12.50%missed diagnosis rate and a large number of false positives.(3)In this study population,NGS results were completely consistent with traditional tertiary screening,and compared with conventional thalassemia genetic testing,an additional 3 cases of unusual types and 4 cases of rareβ-globin gene point mutations of unknown significance were detected.Conclusion One-time NGS screening significantly reduces the rate of missed diagnosis in thalassemia gene carriers during the prenatal period,and provides additional detection of rare types and unknown genetic variants.
作者
黎文雅
孙波
赵卫华
叶家秀
周凯苏
周娟芳
LI Wenya;SUN Bo;ZHAO Weihua;YE Jiaxiu;ZHOU Kaisu;ZHOU Juanfang(Shenzhen Second People's Hospital,The First Affiliated Hospital of Shenzhen University,Guangdong Shenzhen 518035;Shenzhen Bao'an Maternal and Child Health Hospital,Bao'an Maternal and Child Health Hospital Affiliated to Jinan University School of Medicine,Guangdong Shenzhen 518121)
出处
《深圳中西医结合杂志》
2024年第7期30-34,共5页
Shenzhen Journal of Integrated Traditional Chinese and Western Medicine
基金
深圳市卫生健康委学科建设能力提升项目(SZXJ2017001)。
关键词
地中海贫血
基因筛查
高通量测序
孕妇
Thalassemia
Genetic screening
Next-generation sequencing
Pregnant woman
