應用次世代定序進行胎兒基因檢測之分析

Abstract

臺灣近年來面臨少子化及生育年齡高齡化之影響，對於胎兒的基因及健康重視程度提升，也促使政府重視產前檢驗的福利政策，隨著產檢醫療及檢驗技術的進步，除了傳統染色體檢驗外，更可以應用次世代定序檢驗更多疾病，透過其高通量、快速分析和高靈敏度的特性，用以預防疾病對於家庭功能、經濟系統及醫療資源造成的衝擊。 我們應用次世代定序技術進行胎兒基因分析，並根據臺灣人相對常見的疾病基因變異，設計成390個基因的檢驗組套，以其中101個基因為主要檢測組套，剩餘289個基因為次要檢測組套。回溯2021年至2023年間，共1830筆基因檢測結果，833筆無異常、 893筆異常帶因，94筆致病異常，依照基因遺傳模式、數量分組統計及討論。 統計結果顯性表現疾病25筆、隱性表現疾病為29筆、性聯表現疾病39筆及粒線體表現1筆，疾病包括聽力損傷、外觀、代謝性、器官發育、各項發展異常之疾病等，基因型別多數與國人常見之變異吻合，接著我們透過父母親的基因檢測結果，確認胎兒基因變異的形式，用以作為臨床診斷之參考。此外部分異常疾病更為產前超音波無法偵測之問題，對於臨床診斷和遺傳諮詢提供重要的資訊。 透過兩年來基因檢驗結果的整理，並分析基因型別後，我們認為此項檢測具有價值性，即使檢驗裡仍有許多需要克服的問題，但能提供家庭及早發現、預防、準備及決定，同時也對於產前醫療提供更多資訊參考。我們希望可以將此研究作為未來效益分析的基礎，並能建置完整的遺傳諮詢流程，讓產前檢驗更加完善。

In recent years, Taiwan has faced the impacts of a declining birth rate and an increase in the age of childbearing, leading to greater emphasis on fetal genetics and health. This has prompted the government to prioritize prenatal examination welfare policies. With advancements in prenatal medical care and testing technology, in addition to traditional chromosomal testing, next-generation sequencing (NGS) can be used to detect a wider range of diseases. The high throughput, rapid analysis, and high sensitivity of NGS help prevent diseases' impact on family functions, economic systems, and medical resources. We applied NGS technology to analyze fetal genes, designing a panel of 390 genes based on the relatively common genetic variations in the Taiwanese population. Of these, 101 genes were used as the primary gene set, while the remaining 289 genes formed the secondary gene set. From 2021 to 2023, we analyzed a total of 1,830 genetic test results: 833 were normal, 893 carried abnormal variations, and 94 were pathogenic abnormalities. The results were categorized and discussed according to genetic inheritance patterns and quantities. Statistical results showed 25 cases of dominant diseases, 29 cases of recessive diseases, 39 cases of X-linked diseases, and 1 case of mitochondrial disease. The diseases detected included hearing loss, appearance, metabolic disorders, organ development issues, and various developmental abnormalities. The majority of genotypes matched the common variations found in the Taiwanese population. We further verified the forms of fetal genetic variations through parental genetic test results, providing important references for clinical diagnosis. Some abnormalities detected were beyond the reach of prenatal ultrasound, offering critical information for clinical diagnosis and genetic counseling. Through the compilation and analysis of genetic test results over the past two years, we believe that this testing method is valuable. Despite the many challenges that still need to be addressed, it can help families to detect, prevent, prepare, and make informed decisions early on. It also provides more information for prenatal medical care. We hope this study can serve as a foundation for future benefit analysis and the establishment of a comprehensive genetic counseling process, improving the overall prenatal examination framework.