遗传性眼病致病基因突变分析中应重视临床表型的评估

Clinical phenotype assessment is very important in mutation analysis for patients with hereditary eye disease

一代测序（Sanger测序）技术可对候选基因进行测序分析，其测序读长较长，准确性高，是过去三四十年里常用的基因突变分析方法，但因其存在测序通量小及成本高等缺点，限制了其在具有高度遗传异质性疾病及大样本量基因突变分析中的应用。二代测序（NGS）技术是2005年以来发展起来的在临床上广泛应用的基因测序技术，测序通量高，费用较低，自动化程度高，为遗传性眼病的基因诊断带来了很大的便利。但实际上，单基因遗传性眼病具有高度遗传异质性和临床异质性，在应用NGS技术对遗传性眼病的分析过程中过度依赖基因突变分析技术而忽略患者复杂临床表型的评估可能在基因测序检测方法的选择上出现偏差，造成检测结果判断的失误或给患者带来经济负担。目前，单基因遗传性眼病基因突变分析方法主要是NGS分析结合Sanger测序验证，在此过程中应重视患者临床表型的准确评估，以确保准确选择基因检测方法和合理判定致病基因突变。

Sanger sequencing technology is the most commonly used method for genetic analysis in inherited eye disease in the past few decades on account of its long DNA sequencing read length and high accuracy. However, application of this method is limited in genetically heterogeneous diseases because of the high economic and time cost. Next generation sequencing （NGS） technology is a high-throughput, cost-effective, and highly automated method which has been widely used since 2005. Although NGS is especially suitable for studies on genetically heterogeneous inherited eye disease,overdependence on the technique itself and neglect of the assessment of the phenotype may lead to misjudgment of the testing results and higher economic burden for the patients. So far,the most common method on researches of monogenic inherited eye disease is to combine NGS and Sanger sequencing technique. Precise evaluation of the clinical phenotype of patients is very important, as it is related with selection of detection methods and determination of disease-causing mutations.