Center for Maternal-Fetal Precision Medicine, University of California, San Francisco, San Francisco, CA, USA; Department of Surgery, University of California, San Francisco, San Francisco, CA, USA.
Center for Maternal-Fetal Precision Medicine, University of California, San Francisco, San Francisco, CA, USA; Department of Psychiatry and Behavioral Sciences, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA.
Am J Surg. 2022 Jan;223(1):182-186. doi: 10.1016/j.amjsurg.2021.07.016. Epub 2021 Jul 20.
To identify genes associated with congenital diaphragmatic hernia (CDH) to help understand the etiology and inform prognosis.
We performed exome sequencing on fetuses with CDH and their parents to identify rare genetic variants likely to mediate risk. We reviewed prenatal characteristics and neonatal outcomes.
Data were generated for 22 parent-offspring trios. Six Likely Damaging (LD) variants were identified in five families (23 %). Three LD variants were in genes that contain variants in other CDH cohorts (NR2F2, PTPN11, WT1), while three were in genes that do not (CTR9, HDAC6, TP53). Integrating these data bolsters the evidence of association of NR2F2, PTPN11, and WT1 with CDH in humans. Of the five fetuses with a genetic diagnosis, one was terminated, two underwent perinatal demise, while two survived until repair.
Exome sequencing expands the diagnostic yield of genetic testing in CDH. Correlating CDH patients' exomes with clinical outcomes may enable personalized counseling and therapies.
为了鉴定与先天性膈疝（CDH）相关的基因，以帮助了解病因并提供预后信息。
我们对患有 CDH 的胎儿及其父母进行外显子组测序，以鉴定可能介导风险的罕见遗传变异。我们回顾了产前特征和新生儿结局。
为 22 个父母-子女三联体生成了数据。在五个家庭（23%）中发现了六个可能具有破坏性（LD）的变异。三个 LD 变异位于包含其他 CDH 队列中变异的基因中（NR2F2、PTPN11、WT1），而三个位于不包含变异的基因中（CTR9、HDAC6、TP53）。整合这些数据增强了 NR2F2、PTPN11 和 WT1 与人类 CDH 相关的证据。在接受基因诊断的五名胎儿中，一名被终止妊娠，两名在围产期死亡，两名存活至修复。
外显子组测序扩大了 CDH 基因检测的诊断效果。将 CDH 患者的外显子组与临床结局相关联，可能能够实现个性化咨询和治疗。
