Department of Medical and Molecular Genetics, Dongguan Institute of Pediatrics, Dongguan, Guangdong, China.
CapitalBio Genomics Co. Ltd, Dongguan, Guangdong, China.
J Pak Med Assoc. 2020 Oct;70(10):1789-1794. doi: 10.5455/JPMA.28637.
The application of next-generation sequencing (NGS) will greatly promote the screening and diagnosis of genetic diseases. This study aimed to implement and validate a targeted NGS panel for genetic screening of over fifty types of genetic disorders in newborns.
A targeted gene panel consisting of 104 known genes related to genetic diseases with a target size of 347.8 kb was designed. Genes were selected through reference to databases including HGMD, OMIM, GeneReviews®, and Genetic Home Reference, and the latest peer-reviewed publications associated with the genetics of hereditary diseases.
The average coverage for all targeted exons was 596X, and the mean targeted region coverage of 1X, 10X, 20X and 50X reads for each sample were 99.8%, 99.2%, 98.8%, and 95.3%, respectively. The panel showed 100% consistency in detecting 8 pathogenic insertion/deletion (indels) variants ranging from 1 to 16 bp in size and 20 pathogenic single-nucleotide variations (SNVs) across 32 samples previously confirmed by Sanger sequencing.
A dried blood spot (DBS)-based targeted NGS panel for efficient genetic screening of a wide variety of genetic diseases in newborns was developed and evaluated. Furthermore, our panel will contribute to providing accurate diagnosis for genetic disorders and will be helpful for gene therapy for specific diseases.
下一代测序（NGS）的应用将极大地促进遗传疾病的筛查和诊断。本研究旨在实施和验证一种针对新生儿 50 多种遗传疾病的靶向 NGS panel 进行遗传筛查。
设计了一个靶向基因panel，包含 104 个与遗传疾病相关的已知基因，目标大小为 347.8 kb。通过参考 HGMD、OMIM、GeneReviews®和 Genetic Home Reference 等数据库以及与遗传性疾病遗传学相关的最新同行评议出版物，选择基因。
所有靶向外显子的平均覆盖率为 596X，每个样本的靶向区域覆盖率分别为 1X、10X、20X 和 50X 的平均值为 99.8%、99.2%、98.8%和 95.3%。该 panel 在检测大小为 1 到 16bp 的 8 种致病性插入/缺失（indels）变异和 32 个经 Sanger 测序证实的样本中的 20 种致病性单核苷酸变异（SNVs）方面具有 100%的一致性。
开发并评估了一种基于干血斑（DBS）的靶向 NGS panel，用于对新生儿进行广泛的遗传疾病进行高效的遗传筛查。此外，我们的 panel 将有助于为遗传疾病提供准确的诊断，并有助于针对特定疾病的基因治疗。
