1例携带NIPBL基因新变异的德朗热综合征

A Case of Cornelia de Lange Syndrome Harboring a Novel Mutation of NIPBL

目的明确1例特殊面容、生长迟缓、肢体异常患儿的致病基因变异及来源,为疾病的诊断和遗传咨询提供依据。方法采集患儿及其父母外周血样并提取DNA,进行全外显子组测序检测,结合生物信息学分析方法进行数据分析,获取致病性基因变异位点,最后利用Sanger测序进行验证。结果全外显子组测序结果显示位于5号染色体的NIPBL基因42号外显子上发现错义变异c.7177T>C(p.Ser2393Pro),该变异各人群数据库中未见收录。经父母Sanger验证显示,父母均无携带,属于新发变异(de novo mutation)。结合临床症状和基因检测结果,该患儿确诊为经典型德朗热综合征(Cornelia de Lange syndrome,CdLS)。结论对于特殊面容、生长迟缓、肢体异常的患儿应考虑CdLS可能,并常规进行基因检测明确诊断,有助于患儿随访管理、预后评估及遗传咨询等。

Objective To identify the mutation and origin of causal genes in a child with unusual facies,growth retardation and limb abnormalities,and to provide a basis for diagnosis and genetic counseling of the disease.Methods Peripheral blood samples were collected from the child and his parents for the extraction of DNA.Whole-exome sequencing and bioinformatics analysis were performed to identify the pathogenic gene mutations.Finally,Sanger sequencing was used to verify the results.Results Whole-exome sequencing showed a missense mutation(c.7177T>C,p.Ser2393Pro)in exon 42 of the NIPBL gene on chromosome 5.The mutation was not included in all population databases.Sanger sequencing indicated that the mutation was a de novo mutation,which was not derived from his parents.Clinical symptoms combined with genetic testing results confirmed that the child had a classic Cornelia de Lange syndrome(CdLS).Conclusion CdLS should be considered in children with unusual facies,growth retardation and limb abnormalities.Furthermore,genetic testing should be routinely performed to confirm the diagnosis.It is helpful for the follow-up management,prognosis assessment and genetic counseling.