拷贝数变异在遗传病诊断和遗传咨询中的应用现状

Current Status of Copy Number Variation in the Diagnosis of Genetic Diseases and Genetic Counseling

摘要: 遗传病是一类人群患病率低、病例分散、机制复杂、病情严重的疾病。该类疾病大多由遗传缺陷引起，对患病家属及临床带来巨大挑战。遗传检测技术成为诊断遗传病的关键手段之一。遗传检测技术主要为基因组拷贝数变异(Copynumbervariations, CNV)检测。基因组拷贝数变异是由基因组发生重排导致的拷贝数增加或减少，主要表现为亚显微水平的微缺失和微重复，与遗传性疾病的发展密不可分。拷贝数变异检测显著提高多种遗传病的检出率，然而在解读某些特殊的拷贝数变异方面，临床仍存在巨大挑战。遗传咨询的意义主要体现在向患者及家属解释拷贝数变异的结果、风险评估及再生育计划等。本文将从遗传病的概述，分子检测手段，报告解读、临床应用及遗传咨询方面进行综述。

Abstract: Genetic disorders represent a group of diseases characterized by low population prevalence, scattered cases, complex pathogenic mechanisms, and severe clinical manifestations. Most of these disorders are caused by inherited genetic defects, posing significant challenges to affected families and clinical management. Genetic testing has emerged as a crucial diagnostic approach, with copy number variation (CNV) detection serving as a primary methodology. CNVs result from genomic rearrangements leading to DNA segment gains or losses, primarily manifesting as submicroscopic deletions and duplications that are intrinsically linked to the pathogenesis of genetic diseases. While CNV detection has significantly improved diagnostic yields for various genetic disorders, substantial challenges remain in interpreting certain complex CNVs. Genetic counseling plays a pivotal role in explaining CNV results to patients and families, facilitating risk assessment and reproductive planning. This review comprehensively examines the characteristics of genetic disorders, molecular diagnostic techniques, clinical interpretation of test reports, practical applications, and genetic counseling considerations.