血红蛋白病的人群筛查和产前诊断

Population-based carrier screening and prenatal diagnosis for hemoglobinopathy

血红蛋白病是最常见的人类孟德尔遗传病之一,主要包括异常血红蛋白、地中海贫血(地贫)二类疾病。该病主要分布在包括中国南方在内的世界上热带和亚热带地区,由于高发地区人群频率高,该病患儿出生的人群负荷是世界公认的公共卫生问题,通过产前诊断阻止患儿出生是目前首选的预防措施。本报告首先介绍了血红蛋白病的遗传流行病学和分子基础知识,主要聚焦于中国人群的致病基因突变谱及遗传修饰基因变异,后者是近几年研究阐明的影响单基因病临床表型变异的重要遗传因素。本报告还进一步阐述了血红蛋白病的预防策略和措施,并通过在广西实施的大规模人群防控计划的经验,阐述了传统检测技术方法在疾病预防中的应用,以及基于二代测序的新技术在血红蛋白病的快速临床诊断和分子筛查中的应用价值。

Hemoglobinopathies are one of the most common human Mendelian disorders, including two distinct sub-groups of genetic defects, abnormal hemoglobin and thalassemias. The inherited hemoglobin disorders are widely distributed in tropical and subtropical regions in the world. Burden of hemoglobinopathies is becoming a public health issue due to high incidence of affected children in the disease-endemic regions of the world. A priority measure is to conduct prenatal diagnosis for at-risk couples aimed at reducing the birth of affected fetuses. The report describes some updated knowledge on the genetic epidemiology and molecular basis for hemoglobinopathies, particularly focused on the Chinese-specific spectrum of mutations in HBA/HBB and modifier variants that are defined as important modulators contributed to disease phenotypes. The report provides a brief demonstration of the hemoglobinopathy prevention program and shares some experiences in implementing traditional methods to this program in Guangxi. Additionally, the report discusses next generation sequencing (NGS)-based rapid clinical diagnosis and molecular screening for this inherited disorder.