Genomic Sequencing for Newborn Screening: Results of the NC NEXUS Project
Genomic Sequencing for Newborn Screening: Results of the NC NEXUS Project
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DOI：
10.1016/j.ajhg.2020.08.001
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发表时间：
2020-10-01
影响因子：
9.8
通讯作者：
Berg, Jonathan S.
中科院分区：
文献类型：
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作者：
Roman, Tamara S.;Crowley, Stephanie B.;Berg, Jonathan S.
新生儿筛查（NBS）是在20世纪60年代建立的一项公共卫生计划，对于促进某些医疗状况的检测至关重要，早期干预可以预防严重的，危及生命的健康问题。基因组测序可以潜在地扩大对罕见遗传性疾病的筛查，但许多问题围绕着它可能用于这一目的。我们在北卡罗来纳州新生儿外显子组测序通用筛查（NC NEXUS）项目中检查了外显子组测序（ES）在NBS中的应用，比较了ES在筛查和诊断背景下的产率。我们招募了健康新生儿和患有代谢性疾病或听力损失的儿童（共106名参与者）。ES在17名代谢紊乱儿童中的15名（88%）和28名听力损失儿童中的5名（18%）中证实了参与者的基础诊断。我们在四名参与者中发现了标准NBS无法检测到的可操作结果。一部分父母有资格获得关于儿童期发病的低或无临床可操作性的疾病、临床可操作的成人期发病的疾病和常染色体隐性疾病的携带者状态的额外信息。我们在两名儿童中发现了与遗传性乳腺癌和/或卵巢癌相关的致病性变异，在一名儿童中发现了与Lowe综合征相关的基因中的可能致病性变异，并且平均每个儿童有1.8个可报告的变异用于携带者结果。这些结果突出了使用基因组测序进行NBS的好处和局限性，以及在未来的精准医学方法中使用这种技术的挑战。
Newborn screening (NBS) was established as a public health program in the 1960s and is crucial for facilitating detection of certain medical conditions in which early intervention can prevent serious, life-threatening health problems. Genomic sequencing can potentially expand the screening for rare hereditary disorders, but many questions surround its possible use for this purpose. We examined the use of exome sequencing (ES) for NBS in the North Carolina Newborn Exome Sequencing for Universal Screening (NC NEXUS) project, comparing the yield from ES used in a screening versus a diagnostic context. We enrolled healthy newborns and children with metabolic diseases or hearing loss (106 participants total). ES confirmed the participant's underlying diagnosis in 15 out of 17 (88%) children with metabolic disorders and in 5 out of 28 (similar to 18%) children with hearing loss. We discovered actionable findings in four participants that would not have been detected by standard NBS. A subset of parents was eligible to receive additional information for their child about childhood-onset conditions with low or no clinical actionability, clinically actionable adult-onset conditions, and carrier status for autosomal-recessive conditions. We found pathogenic variants associated with hereditary breast and/or ovarian cancer in two children, a likely pathogenic variant in the gene associated with Lowe syndrome in one child, and an average of 1.8 reportable variants per child for carrier results. These results highlight the benefits and limitations of using genomic sequencing for NBS and the challenges of using such technology in future precision medicine approaches.