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目的:分析一例临床表现疑似德朗热综合征的男性患儿的遗传学病因。方法:采集患儿的外周血样进行染色体核型分析，基因组拷贝数变异测序(copy number variation sequencing，CNV-seq)检测及全外显子组测序(whole exome sequencing，WES)检测。同时采集其父母外周血样，对患儿核型、基因组拷贝数、全外显子异常的疑似致病性变异行家系验证。结果:患儿临床表现为发育落后、小头畸形、上睑下垂、小颌畸形、低耳位，临床诊断为疑似德朗热综合征(Cornelia de Lange syndrome，CdLS)。其染色体核型分析及CNV-seq检测结果未见异常，全外显子组测序检测显示存在5个杂合变异和1个X染色体半合子变异。根据遗传模式和家系验证结果，n SMC1A基因c.3500T>C(p.Ile1167Thr)半合子变异为患儿临床表现的遗传学病因。该变异在dbSNP数据库及gnomAD数据库中未见收录，PolyPhen2, PROVEAN, SIFT软件预测为有害变异，PhastCons保守性预测为保守。ACMG变异分类标准证据支持为PM2、PP2和PP3。n 结论:新发现的n SMC1A基因c.3500T>C(p.I1167T)错义变异为患儿临床表现的遗传学病因，该患儿为CdLS综合征Ⅱ型(温和型)。本研究的结果丰富了CdLS综合征Ⅱ型的变异谱，为临床咨询提供了数据支持。n “,”Objective:To explore the genetic etiology of a neonate with suggestive features of Cornelia de Lange Syndrome (CdLS).Methods:Chromosome karyotyping, copy number variation sequencing (CNV-seq) and whole exome sequencing (WES) were carried out for the child. Meanwhile, peripheral venous blood samples were taken from his parents for verifying the suspected pathogenic variants detected in the child.Results:The child has exhibited developmental delay, microcephaly, ptosis, micrognathia, and low ear setting, and was suspected as CdLS. No abnormality was found by karyotyping and CNV-seq analysis. WES has detected 5 heterogeneous variants and 1 hemizygous variant on the X chromosome. Combining the genetic pattern and result of family verification, a hemizygous C. 3500T>C (p.ile1167thr) of then SMC1A gene was predicted to underlay the clinical manifestations of the patient. This variant was not recorded in the dbSNP and gnomAD database. PolyPhen2, Provean, SIFT all predicted the variant to be harmful, and PhastCons conservative prediction is was a conservative mutation. ACMG variant classification standard evidence supports are PM2, PP2, and PP3.n Conclusion:The novel c. 3500T>C (p.Ile1167Thr) missense mutation of then SMC1A gene probably underlay the genetic etiology of CdLS in this child. Above results has enriched the mutation spectrum of CdLS type II, and facilitated clinical counseling for this family.n