Objective To explore the genetic basis for an infant featuring developmental delay,hand deformity and hypertonia of extremities.Methods Clinical data and peripheral blood samples of the proband and her parents were collected.Following DNA extraction,potential mutations were screened on an Ion PGM platform using a gene panel.Suspected mutation was verified by PCR and Sanger sequencing.Results A novel heterozygous nonsense mutation,c.2521C>T(p.R841X),was identified in the N IPBL gene.The mutation may cause premature termination of translation of the adhesion protein loading factor at 841st amino acids.The same mutation was not found in her parents and 931 healthy controls,and was absent from public databases including ExAC and 1000G.Bioinformatic analysis suggested the mutation to be disease causing.Conclusion The c.2521C> T (p.R841X)mutation of the N IPBL gene probably underlies the Cornelia De Lange syndrome in the infant.Prenatal diagnosis may be provided to this family upon their subsequent pregnancy.%目的 分析一例发育落后、双手畸形、四肢肌张力高的婴儿的遗传学病因并帮助确诊及指导家庭生育.方法 收集该家系患儿和正常表型父母的临床资料,采集外周血提取基因组DNA.通过高通量测序法筛查、Sanger测序法验证N IPBL基因新突变位点.检索该突变在人群中发生的频率,参考美国医学遗传学和基因组学学会指南判断检出突变的致病性.患儿母亲再次怀孕时进行产前诊断.结果 该患儿存在N IPBL基因c.2521C＞T(p.R841X)无义突变,导致其编码的黏连蛋白加载因子在第841位氨基酸处翻译提前终止.患儿父母和931例对照人群中未检测到相同变异.ExAC、1000G、dbSNP等数据库中未记录该变异的频率.综合分析认为该变异为有害突变.结论 N IPBL基因c.2521C＞T(p.R841X)无义突变是导致患儿德朗热综合征1型的致病原因,据此突变位点可进行产前诊断.
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