Butchbach Matthew E R
Center for Applied Clinical Genomics, Nemours Biomedical Research, Nemours Alfred I. duPont Hospital for Children, Wilmington, DE, USA; Center for Pediatric Research, Nemours Biomedical Research, Nemours Alfred I. duPont Hospital for Children, Wilmington, DE, USA; Department of Biological Sciences, University of Delaware, Newark, DE, USA; Department of Pediatrics, Thomas Jefferson University, Philadelphia, PA, USA.
Biomol Detect Quantif. 2016 Aug 8;10:9-14. doi: 10.1016/j.bdq.2016.06.002. eCollection 2016 Dec.
Early-onset rare diseases have a strong impact on child healthcare even though the incidence of each of these diseases is relatively low. In order to better manage the care of these children, it is imperative to quickly diagnose the molecular bases for these disorders as well as to develop technologies with prognostic potential. Digital PCR (dPCR) is well suited for this role by providing an absolute quantification of the target DNA within a sample. This review illustrates how dPCR can be used to identify genes associated with pediatric-onset disorders, to identify copy number status of important disease-causing genes and variants and to quantify modifier genes. It is also a powerful technology to track changes in genomic biomarkers with disease progression. Based on its capability to accurately and reliably detect genomic alterations with high sensitivity and a large dynamic detection range, dPCR has the potential to become the tool of choice for the verification of pediatric disease-associated mutations identified by next generation sequencing, copy number determination and noninvasive prenatal screening.
早发性罕见疾病对儿童医疗保健有重大影响，尽管这些疾病各自的发病率相对较低。为了更好地管理对这些儿童的护理，迅速诊断这些疾病的分子基础以及开发具有预后潜力的技术势在必行。数字PCR（dPCR）通过对样品中的目标DNA进行绝对定量，非常适合这一角色。本综述阐述了dPCR如何用于鉴定与儿童期发病疾病相关的基因、确定重要致病基因和变体的拷贝数状态以及对修饰基因进行定量。它也是一种强大的技术，可跟踪随着疾病进展基因组生物标志物的变化。基于其能够以高灵敏度和大动态检测范围准确可靠地检测基因组改变的能力，dPCR有潜力成为验证通过下一代测序、拷贝数测定和无创产前筛查鉴定出的儿童疾病相关突变的首选工具。
