产前全外显子组测序诊断SMARCA4变异所致Coffin-Siris综合征一例

Diagnosis a fetus with Coffin-Siris syndrome due to variant of SMARCA4 gene by whole exome sequencing

目的:探讨1例拟诊为Coffin-Siris综合征胎儿的临床表型及遗传学病因。方法:对胎儿进行染色体微阵列分析与全外显子组测序,对候选变异进行Sanger测序验证。结果:孕23周发现胎儿侧脑室呈进行性不对称增宽。染色体微阵列分析未见异常,全外显子组测序提示其SMARCA4基因第19外显子存在c.2851G>A(p.G951R)新发杂合变异,判读为致病性变异。结论:对于侧脑室进行性增宽的胎儿应考虑进行基因检测,以明确其遗传学病因及预后。

Objective To explore the clinical phenotype and genetic basis for a fetus suspected for Coffin-Siris syndrome.Methods Chromosomal microarray analysis(CMA)and whole exome sequencing(WES)were carried out for the fetus.Candidate variant was verified by Sanger sequencing.Results Prenatal ultrasound at 23rd gestational week has revealed fetal ventriculomegaly.No abnormality was found by CMA,while WES revealed that the fetus has harbored a de novo heterozygous c.2851G>A(p.G951R)variant of the SMARCA4 gene,which was predicted to be pathogenic.Conclusion Genetic testing should be considered for fetuses featuring progressive widening of lateral cerebral ventricles.