Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine, Cambridge, MA 02139, USA.
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine, Cambridge, MA 02139, USA; Harvard Medical School, Boston, MA 02115, USA.
Am J Hum Genet. 2019 Jan 3;104(1):76-93. doi: 10.1016/j.ajhg.2018.11.016.
Genomic sequencing provides many opportunities in newborn clinical care, but the challenges of interpreting and reporting newborn genomic sequencing (nGS) results need to be addressed for its broader and effective application. The BabySeq Project is a pilot randomized clinical trial that explores the medical, behavioral, and economic impacts of nGS in well newborns and those admitted to a neonatal intensive care unit (NICU). Here we present childhood-onset and actionable adult-onset disease risk, carrier status, and pharmacogenomics findings from nGS of 159 newborns in the BabySeq Project. nGS revealed a risk of childhood-onset disease in 15/159 (9.4%) newborns; none of the disease risks were anticipated based on the infants' known clinical or family histories. nGS also revealed actionable adult-onset disease risk in 3/85 (3.5%) newborns whose parents consented to receive this information. Carrier status for recessive diseases and pharmacogenomics variants were reported in 88% and 5% of newborns, respectively. Additional indication-based analyses were performed in 29/32 (91%) NICU newborns and 6/127 (5%) healthy newborns who later had presentations that prompted a diagnostic analysis. No variants that sufficiently explained the reason for the indications were identified; however, suspicious but uncertain results were reported in five newborns. Testing parental samples contributed to the interpretation and reporting of results in 13/159 (8%) newborns. Our results suggest that nGS can effectively detect risk and carrier status for a wide range of disorders that are not detectable by current newborn screening assays or predicted based on the infant's known clinical or family history, and the interpretation of results can substantially benefit from parental testing.
基因组测序为新生儿临床护理提供了许多机会，但为了更广泛和有效地应用基因组测序，需要解决解释和报告新生儿基因组测序（nGS）结果的挑战。BabySeq 项目是一项探索 nGS 在健康新生儿和新生儿重症监护病房（NICU）入院新生儿中的医学、行为和经济影响的试点随机临床试验。在这里，我们展示了来自 BabySeq 项目 159 名新生儿 nGS 的儿童期发病和可操作性成人发病疾病风险、携带者状态和药物基因组学发现。nGS 显示 159 名新生儿中有 15 名（9.4%）存在儿童期发病疾病风险；这些疾病风险都没有根据婴儿的已知临床或家族史预测到。nGS 还揭示了 85 名新生儿中有 3 名（3.5%）的父母同意接受这一信息的可操作性成人发病疾病风险。隐性疾病和药物基因组学变异的携带者状态分别在 88%和 5%的新生儿中得到报告。在另外 29/32（91%）名 NICU 新生儿和 6/127（5%）名健康新生儿中进行了基于指征的额外分析，这些新生儿后来的表现促使进行了诊断分析。没有发现足以解释指征的变异；然而，在五名新生儿中报告了可疑但不确定的结果。在 159 名新生儿中有 13 名（8%）的新生儿，检测父母样本有助于解释和报告结果。我们的结果表明，nGS 可以有效地检测目前新生儿筛查检测无法检测或根据婴儿已知临床或家族史预测不到的广泛疾病的风险和携带者状态，并且结果的解释可以从父母的检测中获得实质性的收益。
