2020年 · 第100卷第09期

With the development of individualized medicine and the concept of "precision medicine", tumor drug therapy has developed rapidly, and clinical research has gradually discovered and confirmed more gene mutations related to the prediction of drug therapy efficacy^[1]。 Traditional gene mutation detection methods such as Sanger sequencing, pyrosequencing and real-time fluorescence PCR can only detect a single gene or partial exon mutations of a single gene. Using the above traditional gene mutation detection methods to detect multiple genes at the same time, one requires a large sample size, and the second requires a longer detection time and a greater workload. High-throughput sequencing (HTS), or next-generation sequencing (NGS), can sequence millions or even billions of DNA fragments at the same time, and can realize up to hundreds of tumor-related genes at a time at a lower cost. The whole exon and whole genome are tested, and the required sample size does not increase. Due to its advantages in throughput, cost and efficiency, NGS has shown its broad application prospect in somatic gene mutations in solid tumors^[2]。

Genetic diseases are diseases caused by genetic mutations or variations in the number or structure of chromosomes. According to the changes of genetic material, it can be divided into monogenic diseases, polygenic diseases, chromosomal diseases, mitochondrial genetic diseases and somatic genetic diseases^[1]。 At present, more than 6,000 genetic diseases with known molecular basis have been included in the Human Online Mendelian Genetic Database (OMIM)^[2]。 Because of genetic heterogeneity and phenotypic diversity, conventional detection methods such as Sanger sequencing and chromosome chip analysis (CMA) are difficult to meet the needs of clinical applications in terms of cost, throughput and diagnostic sensitivity. In recent years, high-throughput sequencing, or next-generation sequencing (NGS) technology, has been widely used in the field of genetic disease diagnosis because it can sequence multiple genes, even the whole exome and the whole genome at the same time, and has greatly improved the expectation of genetic disease diagnosis^[3]。 However, compared with the previous technology, the detection operation steps based on NGS technology are many, and the requirements of personnel ability are high. Irregular or excessive use may cause unexpected troubles and harm to the subjects and their families. In order to ensure the standardized application of high-throughput sequencing technology in clinical detection of genetic diseases, we should learn from relevant guidelines, standards, norms and authoritative published documents at home and abroad, as well as the Beijing Expert Consensus on Standardized Application of High-throughput Sequencing Technology in Clinical Detection (General Part of the First Edition)^[4](hereinafter referred to as "General Consensus"), Beijing Clinical Laboratory Center, Laboratory Medicine Branch of Beijing Medical Association, Department of Clinical Laboratory Diagnosis of Capital Medical University, and Beijing Medical Laboratory Quality Control and Improvement Center took the lead in drafting the "Beijing Expert Consensus on Clinical Standardized Application of High-throughput Sequencing Technology (First Edition Genetic Diseases Part)". The statements in this consensus are the points discussed and recommended by experts.