Ko Jung Min, Park Kyung Sun, Kang Yeeok, Nam Seong Hyeuk, Kim Yoonjung, Park Inho, Chae Hyun Wook, Lee Soon Min, Lee Kyung A, Kim Jong Won
Department of Pediatrics, Seoul National University Children's Hospital, Seoul National University College of Medicine, Seoul, Korea.
SD Genomics Co., Ltd., Seoul, Korea.
Yonsei Med J. 2018 Jul;59(5):652-661. doi: 10.3349/ymj.2018.59.5.652.
We developed a new workflow design which included results from both biochemical and targeted gene sequencing analysis interpreted comprehensively. We then conducted a pilot study to evaluate the benefit of this new approach in newborn screening (NBS) and demonstrated the efficiency of this workflow in detecting causative genetic variants.
Ten patients in Group 1 were diagnosed clinically using biochemical assays only, and 10 newborns in Group 2 were diagnosed with suspected inherited metabolic disease (IMD) in NBS. We applied NewbornDiscovery (SD Genomics), an integrated workflow design that encompasses analyte-phenotype-gene, single nucleotide variant/small insertion and deletion/copy number variation analyses along with clinical interpretation of genetic variants related to each participant's condition.
A molecular genetic diagnosis was established in 95% (19/20) of individuals. In Group 1, 13 and 7 of 20 alleles were classified as pathogenic and likely pathogenic, respectively. In Group 2, 11 and 6 of 17 alleles with identified causative variants were pathogenic and likely pathogenic, respectively. There were no variants of uncertain significance. For each individual, the NewbornDiscovery and biochemical analysis results reached 100% concordance, since the single newborn testing negative for causative genetic variant in Group 2 showed a benign clinical course.
This integrated diagnostic workflow resulted in a high yield. This approach not only enabled early confirmation of specific IMD, but also detected conditions not included in the current NBS.
我们开发了一种新的工作流程设计，该设计综合解读了生化分析和靶向基因测序分析的结果。然后，我们进行了一项试点研究，以评估这种新方法在新生儿筛查（NBS）中的益处，并证明了该工作流程在检测致病基因变异方面的效率。
第1组的10名患者仅通过生化检测进行临床诊断，第2组的10名新生儿在新生儿筛查中被诊断为疑似遗传性代谢疾病（IMD）。我们应用了NewbornDiscovery（SD基因组学公司），这是一种综合的工作流程设计，涵盖了分析物-表型-基因、单核苷酸变异/小插入和缺失/拷贝数变异分析，以及与每个参与者病情相关的基因变异的临床解读。
95%（19/20）的个体建立了分子遗传学诊断。在第1组中，20个等位基因中的13个和7个分别被分类为致病和可能致病。在第2组中，17个已鉴定出致病变异的等位基因中，11个和6个分别为致病和可能致病。没有意义不明确的变异。对于每个个体，NewbornDiscovery和生化分析结果的一致性达到100%，因为第2组中致病基因变异检测为阴性的单一新生儿表现出良性临床病程。
这种综合诊断工作流程产生了很高的诊断率。这种方法不仅能够早期确诊特定的IMD，还能检测出当前新生儿筛查未涵盖的病症。
