基于ACMG指南进行遗传变异致病性评估的策略研究
1. 苏州亿康医学检验有限公司, 医学遗传学部, 江苏苏州 215021
2. 昆明医科大学第一附属医院, 生殖遗传科, 云南昆明 650032
| 摘 要： | 随着高通量测序（Next-generation sequencing, NGS）、高分辨率染色体结构变异检测及三代测序等技术的发展，针对特殊遗传疾病患者的致病性变异检测数量越来越多，大量的新的变异被发现，但如何确定患者表型直接相关的致病性变异是当前难题。上述变异需要经过特定的生物信息学分析，再基于美国医学遗传学会与基因组学学会（The American College of Medical Genetics Genomics and the Association for Molecular Pathology, ACMG-AMP）制定的孟德尔遗传变异解读和指南进行遗传变异分类和解读是当前的热点和难点。针对上述问题，团队根据研究经验和指南，整理突变位点的评估原则、思路、数据库和网址等信息，对基于ACMG规则指导下的遗传变异分类流程进行介绍，以期帮助临床医务人员进行遗传变异分类评估和遗传报告解读，最终使得更多基于基因组序列信息的特殊临床表型患者的个体化遗传评估。 |
| 关 键 词： | ACMG; 遗传变异分类; 策略; 流程 |
| DOI： | 10.57237/j.mrf.2023.01.002 |
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收稿日期: 2022-09-30
接受日期: 2022-11-18
在线出版日期: 2023-02-16
Countermeasure on Evaluation for Pathogenicity of Variation with ACMG Guidelines
1. Department of Medical Genetics, Yikon Genomics Company, Ltd, Suzhou 215021, China
2. Department of Reproduction and Genetics, the First Affiliated Hospital of Kunming Medical University, Kunming 650032, China
| Abstract: | With the development of high-throughput sequencing (Next-generation sequencing, NGS), high-resolution chromosomal structure mutation detection, long-read sequencing and other technologies, a number of pathogenic variants were detected for patients with special genetic diseases rapidly, and new variants were discovered more and more from the patients and their family individuals. However, the evaluation and genetic consulting were main challenge for clinic staff on the uncertain relationship between the new detected variations and disease. And the evaluation of the relationships between the genetic variation and disease were challenged for the clinical doctors on how to explain the genetic reports to the patients correctly. Thus, performing evaluation for the function of the rare genetic variations in disease diagnose with the guideline of the American College of Medical Genetics Genomics and the Association for Molecular Pathology (ACMG-AMP) were necessary. In this work, the principles, ideas, databases and URLs of the relevant variations were introduced according to the research experience and relevant guidelines, the experience of our team with the classification process of genetic variants basing on the guidance of ACMG rules would benefit for helping clinical staff to evaluate the genetic variants classification and genetic consulting, and finally performing the personalized patients diagnosis and treatment based on genome sequence information and special clinical phenotypes for the genetic disease. |
| Keywords: | ACMG; Classification of Genetic Variants; Countermeasure; Process |
基金
| 1. | 上海市胚胎源性疾病重点实验室开放课题 (She2020006) |
| 2. | 云南省卫生健康委员会高层次医学学科带头人 (D-2017007) |
| 3. | 云南省高层次人才培养职称计划“名医专项” (RLMY20200017) |
| 4. | 国家自然科学基金项目 (82160281) |
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