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Abstract：
Exome sequencing (ES) enhanced the diagnostic yield of genetic testing, but has also increased the possibility of uncertain findings. Prenatal ES is increasingly being offered after a fetal abnormality is detected through ultrasound. It is important to know how to handle uncertainty in this particularly stressful period. This systematic review aimed to provide a comprehensive overview of guidelines available for addressing uncertainty related to prenatal chromosomal microarray (CMA) and ES. Ten uncertainty types associated with prenatal ES and CMA were identified and defined by an international multidisciplinary team. Medline (all) and Embase were systematically searched. Laboratory scientists, clinical geneticists, psychologists, and a fetal medicine specialist screened the papers and performed the data extraction. Nineteen papers were included. Recommendations generally emphasized the importance of trio analysis, clinical information, data sharing, validation and re-analysis, protocols, multidisciplinary teams, genetic counselling, whether to limit the possible scope of results, and when to report particular findings. This systematic review helps provide a vocabulary for uncertainties, and a compass to navigate uncertainties. Prenatal CMA and ES guidelines provide a strong starting point for determining how to handle uncertainty. Gaps in guidelines and recommendations were identified and discussed to provide direction for future research and policy making.
摘要：
外显子组测序（ES）提高了基因检测的诊断率，但也增加了不确定结果的可能性。在通过超声检测到胎儿异常后，越来越多地提供产前ES。重要的是要知道如何在这个特别紧张的时期处理不确定性。本系统综述旨在提供可用于解决与产前染色体微阵列（CMA）和ES相关的不确定性的指南的全面概述。由国际多学科小组确定并定义了与产前ES和CMA相关的十种不确定性类型。系统地搜索了Medline（全部）和Embase。实验室科学家,临床遗传学家，心理学家,胎儿医学专家筛选了论文并进行了数据提取。其中包括19篇论文。建议普遍强调三重奏分析的重要性,临床信息，数据共享,验证和重新分析，协议,多学科团队，遗传咨询,是否限制可能的结果范围，以及何时报告特定的发现。这种系统的回顾有助于提供不确定性的词汇，和指南针导航不确定性。产前CMA和ES指南为确定如何处理不确定性提供了一个强有力的起点。确定并讨论了指南和建议中的差距，为未来的研究和政策制定提供了方向。
