PDF(Pubmed)
Abstract：
Whole-exome sequencing is an evolving technology in perinatal diagnosis which allows identification of genetic etiologies that would otherwise go undetermined. In this case report, a 38-year-old Hispanic woman, G5P3013, with a monochorionic diamniotic twin gestation with one fetus displaying significant cranial abnormalities on prenatal ultrasound and magnetic resonance imaging (MRI) of the brain is presented. Fetal anomalies included bilateral ventriculomegaly, absent cavum septum pellucidum, and absent corpus callosum. Diagnostic amniocentesis with chromosome analysis, chromosomal microarray, alpha-fetoprotein, cytomegalovirus, toxoplasmosis, and parvovirus had normal results. Whole-exome sequencing for the anomalous fetus detected a de novo mosaic variant of uncertain significance (VUS) in the calcium/calmodulin dependent serine protein kinase (CASK) gene: c.1963 A > G (p.Asn655Asp). This variant was absent in the normal twin fetus, the mother, and the father. Pathogenic CASK gene mutations are associated with three syndromes: FG syndrome 4, intellectual developmental disorder and microcephaly with pontine and cerebellar hypoplasia (MICPCH), and intellectual developmental disorder with or without nystagmus. Whole-exome sequencing identified a potential etiology for the anomalies detected. The variant likely arose de novo and was the potential cause of the identified cranial abnormalities in one fetus of this monochorionic diamniotic twin gestation. Whole-exome sequencing may provide additional diagnostic utility when standard diagnostic testing is noncontributory.
摘要：
全外显子组测序是围产期诊断中不断发展的技术,其允许鉴定否则将不确定的遗传病因。在这个案例报告中,一位38岁的西班牙裔女性,G5P3013，具有单绒毛膜羊膜双胎妊娠，其中一名胎儿在产前超声和脑部磁共振成像（MRI）上显示出明显的颅骨异常。胎儿异常包括双侧脑室增宽，透明隔腔缺失，并且没有call体。诊断性羊膜穿刺术与染色体分析，染色体微阵列，甲胎蛋白,巨细胞病毒,弓形虫病,细小病毒结果正常。异常胎儿的全外显子组测序在钙/钙调蛋白依赖性丝氨酸蛋白激酶（CASK）基因中检测到不确定意义的从头镶嵌变体（VUS）：c.1963A>G（p。Asn655Asp）。这种变异在正常的双胞胎胎儿中不存在，母亲,和父亲。致病性CASK基因突变与三种综合征相关：FG综合征4，智力发育障碍和小头症伴脑桥和小脑发育不全（MICPCH），有或没有眼球震颤的智力发育障碍。全外显子组测序确定了检测到的异常的潜在病因。该变体可能是从头出现的，并且是该单绒毛膜双胎妊娠的一个胎儿中确定的颅骨异常的潜在原因。当标准诊断测试是非贡献性的时,全外显子组测序可以提供额外的诊断效用。
