高通量测序技术在罕见病分子诊疗中的应用及临床实例分析

罕见病病种繁多，且表型复杂多样，不仅仅体现在疾病间的不同，同一种疾病的不同患者在表型上也可能大相径庭。这种普遍存在的遗传异质性和临床异质性，使罕见病的诊疗极具挑战。近年来，在后人类基因组计划时代，各种测序技术快速发展，使得大规模测序如疾病目标基因集测序、全外显子组测序、全基因组测序等成为了现实。高通量测序技术可实现对多个靶基因进行高通量平行测序，有效节约了成本与时间，越来越广泛地应用到临床疾病分子诊疗领域。分析传统测序技术与高通量测序技术的优缺点，介绍罕见病诊疗中常用的高通量测序策略，并结合临床实例，综述高通量测序技术在罕见病诊疗中的应用。

Application of High-throughput SequencingTechnologies in Molecular Diagnosis and Treatment ofOrphan Diseases and Analysis of Related Clinical Cases

There are a wide variety of rare (orphan) diseases that are characterized by diverse manifestations. This phenotypic diversity is found notonly in different diseases but also in patients suffering from the same disease. Due to the prevalence of genetic and clinical heterogeneity, the diagnosisand treatment of rare diseases is faced with great challenge. In recent years, owing to the fast development of a variety of sequencing technologies inthe post human genome project era, large scale sequencing, such as disease-targeted gene panels, whole exome sequencing and even whole-genomesequencing, has become a reality. High-throughput sequencing (next generation sequencing, NGS) offers a cost- and time-efficient way to detectmutations in many different genes in parallel, and is more and more widely applied in clinical settings for molecular diagnosis and treatment of diseases.In this article, the advantages and disadvantages of traditional sequencing technologies and high throughput sequencing technologies were analyzed,high throughput sequencing strategies commonly applied for the diagnosis and treatment of rare diseases were introduced, and the application of highthroughput sequencing technologies in the diagnosis and treatment of rare diseases was reviewed with clinical cases provided.