美国加州大学伯克利分校Steven E. Brenner、Aashish N. Adhikari和加州大学旧金山分校Jennifer M. Puck研究团队，合作探究了外显子组测序（WES）在新生儿先天性代谢缺陷（IEM）筛查中的应用。相关论文于2020年8月10日发表于《自然-医学》杂志。
研究人员获取了2005年至2013年间在加利福尼亚出生的450万婴儿中几乎所有IEM病例的存档残留干血斑和数据，一些婴儿在串联质谱（MS / MS）筛查中呈阳性但后续测试为阴性。WES的整体灵敏度为88％，特异性为98.4％，而MS/MS分别为99.0％和99.8％，尽管各个IEM的效果各不相同。因此，对于大多数新生儿筛查（NBS） IEM而言，仅WES不够灵敏或不适合作为主要筛选工具。
Title: The role of exome sequencing in newborn screening for inborn errors of metabolism
Author: Aashish N. Adhikari, Renata C. Gallagher, Yaqiong Wang, Robert J. Currier, George Amatuni, Laia Bassaganyas, Flavia Chen, Kunal Kundu, Mark Kvale, Sean D. Mooney, Robert L. Nussbaum, Savanna S. Randi, Jeremy Sanford, Joseph T. Shieh, Rajgopal Srinivasan, Uma Sunderam, Hao Tang, Dedeepya Vaka, Yangyun Zou, Barbara A. Koenig, Pui-Yan Kwok, Neil Risch, Jennifer M. Puck, Steven E. Brenner
Abstract: Public health newborn screening (NBS) programs provide population-scale ascertainment of rare, treatable conditions that require urgent intervention. Tandem mass spectrometry (MS/MS) is currently used to screen newborns for a panel of rare inborn errors of metabolism (IEMs)1,2,3,4. The NBSeq project evaluated whole-exome sequencing (WES) as an innovative methodology for NBS. We obtained archived residual dried blood spots and data for nearly all IEM cases from the 4.5 million infants born in California between mid-2005 and 2013 and from some infants who screened positive by MS/MS, but were unaffected upon follow-up testing. WES had an overall sensitivity of 88% and specificity of 98.4%, compared to 99.0% and 99.8%, respectively for MS/MS, although effectiveness varied among individual IEMs. Thus, WES alone was insufficiently sensitive or specific to be a primary screen for most NBS IEMs. However, as a secondary test for infants with abnormal MS/MS screens, WES could reduce false-positive results, facilitate timely case resolution and in some instances even suggest more appropriate or specific diagnosis than that initially obtained. This study represents the largest, to date, sequencing effort of an entire population of IEM-affected cases, allowing unbiased assessment of current capabilities of WES as a tool for population screening.