Promises, pitfalls and practicalities of prenatal whole exome sequencing.
Promises, pitfalls and practicalities of prenatal whole exome sequencing.
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DOI：
10.1002/pd.5102
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发表时间：
2018-01
影响因子：
3
通讯作者：
Chitty LS
中科院分区：
文献类型：
--
作者：
Best S;Wou K;Vora N;Van der Veyver IB;Wapner R;Chitty LS
产前基因诊断为妊娠和围产期的决策和管理提供信息。在几个小系列中，产前全外显子组测序（WES）方法已经确定了常规测试（核型和微阵列）无法诊断的遗传诊断。在这里，我们回顾了已发表的产前WES研究和最近的会议摘要。确定了31项研究，5个或更多胎儿的诊断率在6.2%和80%之间变化。入选标准的差异以及三例与单例测序方法的差异在很大程度上解释了广泛的诊断率。这些数据表明，诊断率将在胎儿多个异常或在案件预选遗传审查。除了其提高诊断率的能力，我们还探讨了WES在提高对遗传性疾病和致死性胎儿综合征产前表现的理解方面的潜力。我们讨论产前表型的局限性，咨询的挑战，关于变异的不确定意义，偶然和次要的发现，以及技术问题WES。我们回顾了产前WES成为常规检测的一部分之前必须考虑的实际，伦理，社会和经济问题。最后，我们反思了产前基因诊断的潜在未来，包括走向全基因组测序和非侵入性全外显子组和全基因组检测。
Prenatal genetic diagnosis provides information for pregnancy and perinatal decision-making and management. In several small series, prenatal whole exome sequencing (WES) approaches have identified genetic diagnoses when conventional tests (karyotype and microarray) were not diagnostic. Here, we review published prenatal WES studies and recent conference abstracts. Thirty-one studies were identified, with diagnostic rates in series of five or more fetuses varying between 6.2% and 80%. Differences in inclusion criteria and trio versus singleton approaches to sequencing largely account for the wide range of diagnostic rates. The data suggest that diagnostic yields will be greater in fetuses with multiple anomalies or in cases preselected following genetic review. Beyond its ability to improve diagnostic rates, we explore the potential of WES to improve understanding of prenatal presentations of genetic disorders and lethal fetal syndromes. We discuss prenatal phenotyping limitations, counselling challenges regarding variants of uncertain significance, incidental and secondary findings, and technical problems in WES. We review the practical, ethical, social and economic issues that must be considered before prenatal WES could become part of routine testing. Finally, we reflect upon the potential future of prenatal genetic diagnosis, including a move towards whole genome sequencing and non-invasive whole exome and whole genome testing.
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影响因子：
3
作者：
Bayefsky, Michelle J.;White, Amina;Berkman, Benjamin E.
通讯作者：
Berkman, Benjamin E.
影响因子：
3
作者：
Callaway, Jonathan L. A.;Shaffer, Lisa G.;Chitty, Lyn S.;Rosenfeld, Jill A.;Crolla, John A.
通讯作者：
Crolla, John A.
影响因子：
3
作者：
Chitty LS;Mason S;Barrett AN;McKay F;Lench N;Daley R;Jenkins LA
通讯作者：
Jenkins LA
影响因子：
7.2
作者：
通讯作者：
--
DOI：
10.1007/978-3-319-42044-8_14
发表时间：
2016-01-01
期刊：
CIRCULATING NUCLEIC ACIDS IN SERUM AND PLASMA - CNAPS IX
影响因子：
--
作者：
Drury, Suzanne;Mason, Sarah;Chitty, Lyn S.
通讯作者：
Chitty, Lyn S.