PURPOSE We investigated the diagnostic and clinical performance of trio exome sequencing (ES) in parent-fetus trios where the fetus had sonographic abnormalities but normal karyotype, microarray and, in some cases, normal gene-specific sequencing. METHODS ES was performed from DNA of 102 anomalous fetuses and from peripheral blood from their parents. Parents provided consent for the return of diagnostic results in the fetus, medically actionable findings in the parents, and identification as carrier couple for significant autosomal recessive conditions. RESULTS In 21/102 (20.6%) fetuses, ES provided a positive-definitive or positive-probable diagnosis. In 10/102 (9.8%), ES provided an inconclusive-possible result. At least 2/102 (2.0%) had a repeat pregnancy during the study period and used the information from the study for prenatal diagnosis in the next pregnancy. Six of 204 (2.9%) parents received medically actionable results that affected their own health and 3/102 (2.9%) of couples received results that they were carriers for the same autosomal recessive condition. CONCLUSION ES has diagnostic utility in a select population of fetuses where a genetic diagnosis was highly suspected. Challenges related to genetics literacy, variant interpretation, and various types of diagnostic results affecting both fetal and parental health must be addressed by highly tailored pre- and post-test genetic counseling.

中文翻译：

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将胎儿结构异常的外显子组测序整合到临床实践中的方法。


目的 我们研究了三重外显子组测序 (ES) 在亲胎儿三重中的诊断和临床表现，其中胎儿具有超声检查异常，但核型、微阵列正常，在某些情况下，基因特异性测序正常。方法 ES 采用 102 个异常胎儿的 DNA 及其父母的外周血进行。父母同意返回胎儿的诊断结果、父母的医学上可采取行动的发现，以及鉴定为显着常染色体隐性遗传疾病的携带者夫妇。结果 在 21/102 (20.6%) 胎儿中，ES 提供了阳性明确或阳性可能的诊断。在 10/102 (9.8%) 中，ES 提供了一个不确定的可能结果。至少 2/102 (2.0%) 在研究期间重复怀孕，并在下一次怀孕时使用该研究的信息进行产前诊断。 204 名父母中的 6 名 (2.9%) 收到了影响其自身健康的可采取医疗行动的结果，3/102 (2.9%) 的夫妇收到的结果表明他们是相同常染色体隐性遗传病的携带者。结论 ES 对高度怀疑基因诊断的特定胎儿群体具有诊断效用。与遗传学素养、变异解释以及影响胎儿和父母健康的各种类型的诊断结果相关的挑战必须通过高度定制的测试前和测试后遗传咨询来解决。