Cornelia de Lange综合征患儿3例的基因型及表型分析

Analysis of genotypes and phenotypes of three children with Cornelia de Lange syndrome

目的对3例Cornelia de Lange综合征(CdLS)患儿的临床表型及基因检测结果进行分析,明确其致病原因。方法选取2020年3月12日、8月14日、12月5日于甘肃省妇幼保健院医学遗传中心就诊的3例CdLS患儿为研究对象。收集患儿及其父母的临床资料,采集外周血样进行家系高通量测序分析。结果3例患儿的主要临床表现包括发育迟缓、智力低下、特殊面容和其他伴随症状。根据国际诊断共识标准,3例患儿被拟诊为CdLS。通过家系全外显子组测序及生物信息学分析,确诊CdLS。患儿1携带NIPBL基因c.5567_5569delGAAinsTAT错义变异,患儿2携带SMC1A基因c.607A>G错义变异,患儿3携带HDAC8基因c.628+1G>A剪接变异。3例患儿均为新发变异。结论3例患儿均确诊CdLS,并发现了致病基因变异位点,其中NIPBL基因c.5567_5569delGAAinsTAT及HDAC8基因c.628+1G>A变异位点既往未见报道,丰富了CdLS的变异谱。

Objective To analyze the clinical phenotype and results of genetic testing in 3 children with Cornelia de Lange syndrome(CdLS).Methods Clinical data of the children and their parents were collected.Peripheral blood samples of the pedigrees were collected for next generation sequencing analysis.Results The main clinical manifestations of the 3 children have included growth delay,mental retardation,peculiar facies and other accompanying symptoms.Based on the criteria proposed by the International Diagnostic Consensus,all 3 children were suspected for CdLS.As revealed by whole exome sequencing,child 1 has harbored NIPBL gene c.5567_5569delGAA insTAT missense variant,child 2 has harbored SMC1A gene c.607A>G missense variant,and child 3 has harbored HDAC8 gene c.628+1G>A splicing variant.All of the variants were de novo in origin.Conclusion All of the children were diagnosed with CdLS due to pathogenic variants of the associated genes,among which the variants of NIPBL and HDAC8 genes were unreported previously.Above finding has enriched the spectrum of pathogenic variants underlying CdLS.