Ⅱ型Cornelia de Lange综合征胎儿1例的临床表型及致病变异分析

Analysis of clinical phenotype and pathogenic variant of a fetus with Cornelia de Lange syndrome type Ⅱ

目的探讨1例疑似Ⅱ型Cornelia de Lange综合征(CdLS2)的引产胎儿的孕期影像学表现及致病基因变异。方法以2019年9月3日于中国医科大学附属盛京医院妇产科确诊的1例CdLS2胎儿为研究对象。收集胎儿的临床资料和家族史。胎儿引产后应用全外显子组测序筛选致病变异, 用Sanger测序对其进行家系验证。结果孕33周影像学检查提示胎儿透明隔略增宽, 胼胝体显示不清, 额叶体积略小, 皮质变薄, 侧脑室融合畸形, 羊水过多, 胃泡偏小, 消化道闭锁。全外显子组测序发现胎儿携带X染色体SMC1A基因的c.2076delA(p.Lys692Asnfs*27)杂合移码变异, 其父母均未检出相同的变异。结合美国医学遗传学与基因组学学会(ACMG)相关指南变异判断为致病性。结论 CdLS2胎儿的遗传学病因考虑为SMC1A基因c.2076delA变异。上述结果为其父母的遗传咨询及再生育风险评估提供了依据。

Objective To explore the prenatal ultrasonographic features and genetic basis for an abortus suspected for typeⅡCornelia de Lange syndrome(CdLS2).Methods A fetus diagnosed with CdLS2 at the Shengjing Hospital Affiliated to China Medical University on September 3,2019 was selected as the study subject.Clinical data of the fetus and family history was collected.Following induced labor,whole-exome sequencing was carried out on the abortus.Candidate variant was verified by Sanger sequencing and bioinformatic analysis.Results Prenatal ultrasonography(33 weeks of pregnancy)has revealed multiple anomalies in the fetus,which included slightly widened cavity of septum pellucidum,blurred corpus callosum,slightly reduced frontal lobe volume,thin cortex,fusion of lateral ventricles,polyhydramnios,small stomach bubble,and digestive tract atresia.Whole exome sequencing has revealed a heterozygous c.2076delA(p.Lys692Asnfs*27)frameshifting variant in the SMC1A gene,which was found in neither parent and was rated as pathogenic based on the guidelines of American College of Medical Genetics and Genomics(ACMG).Conclusion The CdLS2 in this fetus may be attributed to the c.2076delA variant of the SMC1A gene.Above finding has provided a basis for genetic counseling and assessment of reproductive risk for this family.