建立擴展型帶因者篩檢次世代定序平台應用於體染色體隱性遺傳疾病基因檢測

Establishment of an Expended Carrier Screening Panel for Autosomal Recessive Diseases by Next Generation Sequencing

帶因者篩檢搭配遺傳諮詢能降低隱性遺傳疾病。次世代定序較傳統篩檢法提供高通量且即時偵測大量基因的優勢。本研究中，我們建立了涵蓋63 個基因全外顯子的次世代定序擴展型帶因者篩檢套組，檢測聽損、動作障礙及代謝異常等 40 種隱性遺傳疾病。運用 2 個標準品及已知變異位點的 9 個臨床檢體確立檢驗效能，亦成功找出戊二酸血症第一型家族遺傳之個案。此套組更符合臨床成本效益，且提供足夠的時間做後續遺傳諮詢及行動。

Pre-conception or prenatal carrier screening accompa ny with genetic counseling has contributed to decline the incidences of autosomal recessive and X -linked disorders. However, traditional carrier screening generally focused on specific common m utations in few genes with higher population prevalence. Fortunately, next-generation sequencing provides a comprehensive carrier screening possibility based on its parallel high-throughput scala bility and capacity to detect single nucleotide substitution, insertion/deletion, and copy number variat ion simultaneously. In this study, we designed an expanded carrier screening panel that covering 63 who le protein-coding regions of disease-associated genes which involved in 40 autosomal recessive/X-lin ked disorders, including hereditary deafness, muscular dystrophy, movement disorders and several metabolic syndromes. The panel is intended to apply to highly mixed ethnic Taiwanese population with high diversity of disease spectrum. First, we used two reference samples to demonstrate the accuracy of this panel. Further, disease-causing mutations of nine clinical affected cases with different autosomal rec essive diseases and one family trio with treatable glutaric aciduria type1 were successfully identified. I n summary, compared with current individual genetic test, the NGS based expanded carrier screening panel provides a comprehensive, time-saving and cost-effectiveness strategy for mutation detection and leaves enough time for genetic counseling and further action.