摘要
地中海贫血(地贫)是一种高发的遗传性血红蛋白病,全球约有3.5亿人为地贫基因致病变异携带者,我国南方地区携带率高达10%~25%。通过血液学筛查、热点变异检测以及基于其他技术的罕见型地贫基因检测的"多层级序贯筛诊"模式在地贫防控中取得了显著的成效,但其流程冗繁、受检者及医疗成本高、咨询压力大,存在明显的局限性。单分子实时测序技术以其长读长和准确识别碱基序列的优点,不仅能够拓宽地贫基因变异检测的范围,还能够直接确定α-和β-珠蛋白基因的单体型和结构重排,显著提高检出率,降低误检和漏检率,对于改进地贫基因检测具有革命性意义。随着技术的成熟和成本的下降,单分子实时测序在地贫防控中的应用越来越广泛,目前已积累超过50项临床研究和30万例临床应用数据。本共识基于这些循证证据,通过探讨单分子实时测序在临床地贫基因检测中的应用范围、操作流程及局限性,为临床医师、实验室人员和政策制定者提供参考和指导,助力全生命周期的地贫精准防控。
Thalassemia is a highly prevalent genetic hemoglobinopathy,with approximately 350 million people worldwide carrying variants of the globin genes.The carrier rate in southern China is as high as 10%~25%.The"multi-level sequential screening and diagnosis"approach,which uses hematological screening,hotspot mutation testing,and genetic testing based on other technologies to diagnose rare types of thalassemia,has proven to be highly effective for the prevention and control of thalassemia.However,its cumbersome process,high cost for testing and medical labor,and high demand for genetic consulting have obvious limitations.For its advantages of long reads and accurate identification of sequence variants,Single-Molecule Real-Time(SMRT)Sequencing technology can not only broaden the scope of globin gene mutation detection,but also directly distinguish the haplotypes and structural rearrangements of the α-and β-globin genes,significantly improving the detection rate,reducing false positives and missed detection,and has revolutionized the detection for genetic variants underlying thalassemia.With the maturity of technology and decrease in cost,the application of SMRT sequencing in the prevention and control of thalassemia is becoming increasingly widespread.So far,more than 50 clinical studies and 300,000 clinical application data have been accumulated.Based on these evidence-based studies,this consensus has explored the application scope,workflow,and limitations of employing SMRT sequencing in clinical genetic testing for thalassemia.It aims to provide recommendations and guidance for clinicians,laboratory staff,and policy makers,to support precise prevention and control of thalassemia throughout the full life cycle.
作者
单分子实时测序在地中海贫血精准防控中的临床应用协作组
中国医师协会医学遗传医师分会临床遗传学组
邬玲仟
尹爱华
马燕琳
桂宝恒
Consortium for the Application of Single-Molecule Real-Time Sequencing for the Precise Prevention and Control of Thalassemia;Group of Clinical Genetics,Medical Genetics Branch of Chinese Medical Doctor Association;Wu Lingqian(不详;Research Center for Medical Genetics,School of Life Science,Central South University,Hunan Provincial Key Laboratory for Medical Genetics,MoE Key Laboratory for Rare Pediatric Diseases,Changsha,Hunan 410008,China)
出处
《中华医学遗传学杂志》
2025年第4期385-396,共12页
Chinese Journal of Medical Genetics
基金
国家重点研发计划(2022YFC2703700,2024YFC2707100)
国家自然科学基金(82171856)
广西壮族自治区重点研发计划(桂科AB22035013,AB22035080)。
关键词
单分子实时测序
地中海贫血
专家共识
Single-Molecule Real-Time Sequencing
Thalassemia
Expert consensus
