全外显子组测序发现1例TFAP2A基因新发变异导致的胎儿腮-眼-面综合征

A de novo variant in TFAP2A identified by whole exome sequencing:Branchio-oculo-facial syndrome in a fetus

目的 对1例孕期提示颈背部皱褶厚度(NF)增厚,多囊肾,羊水过少的胎儿流产物进行基因芯片检测以及全外显子组测序以明确其病因。方法 使用超声观察先证者的结构和器官,使用基因芯片(CMA)和全外显子组测序(WES)检测先证者流产物的皮肤组织,提取父母静脉血2mL对胎儿表型相关变异位点进行Sanger测序验证。结果 产前超声提示先证者的NF厚度为9.3 mm,其肾脏表现为肥大和多囊,颈部有水囊瘤,CMA结果无异常,WES发现胎儿TFAP2A基因4号外显子存在可能致病性杂合变异NM_001042425:c.637C>T(p.Arg213Cys),Sanger测序提示该变异为新发变异。结论 结合超声影像和WES的结果,胎儿被诊断为胎儿腮-眼-面综合征(BOFS;OMIM:113620),病因为TFAP2A基因的可能致病性杂合变异。对胎儿全外显子组测序将成为超声发现异常后进行产前诊断的重要手段。

Objective Whole exome sequencing and chromosome microarray analysis were performed on a fetal miscarriage product during pregnancy indicating NF(nuchal fold thickness,NF)thickening,polycystic kidney disease,and oligohydramnios to clarify its etiology.Methods Ultrasound was used to observe the structure and organs of the proband,chromosomal microarray analysis(CMA)was used to detect the amniotic fluid samples,and whole exome sequencing(WES)was used to detect the skin tissue of the proband's abortion.2 mL of parental venous blood was extracted for Sanger sequencing verification of fetal phenotype-related variations.Results Prenatal ultrasound revealed that the NF thickness of the proband was 9.3 mm,and its kidneys presented with hypertrophy and polycystic lesions,with a hydrocystoma in the neck.CMA results showed no abnormalities.WES found a likely pathogenic heterozygous variation in exon 4 of the fetal TFAP2A gene:NM_001042425:c.637C>T(p.Arg213Cys).Sanger sequencing suggested that the variation was a de novo variation.Conclusion Combining ultrasound imaging and WES results,the fetus was diagnosed as branchial ocular facial syndrome(branchio-oculo-facial syndrome,BOFS;OMIM:113620)due to a likely pathogenic heterozygous variation in the TFAP2A gene.Fetal WES will become an important means of prenatal diagnosis after ultrasound images shows abnormities.