摘要 两例患儿（1例男婴、1例女婴）均为婴儿期起病，均以生长缓慢为主诉就诊，均具有特殊面容如毛发浓密、弓形眉、连体眉，睫毛长且弯曲，以及短鼻、小下颌，患儿1伴有先心病（房间隔缺损、肺动脉狭窄）和特殊皮纹（通贯掌），患儿2有腭裂、中重度耳聋。2例患儿的临床特点均提示Cornelia de Lange综合征。应用高通量基因捕获测序技术检测两例患儿Cornelia de Lange综合征的7个已知致病基因NIPBL、SMC1A、SMC3、HDAC8、RAD21、EP300和ANKRD11，Sanger测序法对突变基因进行分析和验证。2例均检测到NIPBL基因的新发突变，1例为移码突变：Exon 45 R2612fsX20（c.7834dupA）；另1例为无义突变：Q169X（c.505C > T）。2例患儿父母的NIPBL基因该位点正常，50例无关健康个体也未发现这两个位点的突变。
Abstract：Both children (one boy and one girl) experienced disease onset in infancy and visited the hospital due to growth retardation. They had unusual facies including thick hair, arched and confluent eyebrows, long and curly eyelashes, short nose, and micrognathia. Patient 1 had congenital heart disease (atrial septal defect and pulmonary stenosis) and special dermatoglyph (a single palmar crease). Patient 2 had cleft palate and moderate-to-severe deafness. Clinical features suggested Cornelia de Lange syndrome in both children. High-throughput sequencing was used to detect the seven known pathogenic genes of Cornelia de Lange syndrome, i.e., the NIPBL, SMC1A, SMC3, HDAC8, RAD21, EP300, and ANKRD11 genes. Sanger sequencing was used to analyze and verify gene mutations. Both patients were found to have novel mutations in the NIPBL gene. One patient had a frameshift mutation in exon 45, c.7834dupA, which caused early termination of translation and produced truncated protein p.R2612fsX20. The other patient had a nonsense mutation, c.505C > T, which caused a premature stop codon and produced truncated protein Q169X. Such mutations were not found in their parents or 50 unrelated healthy individuals.
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