242例颈项透明层增厚胎儿染色体核型联合CNV-Seq检测结果分析

Analysis of the results of chromosomal karyotype combined with CNV-Seq in 242 fetus with increased nuchal translucency

目的 探讨颈项透明层(nuchal translucency, NT)增厚胎儿的遗传学病因及染色体核型分析与CNV-Seq联合检测在NT增厚中的应用价值。方法 选取2017年1月—2022年4月因早孕期NT≥2.5 mm在聊城市东昌府区妇幼保健院产前诊断中心行产前诊断的孕妇242名,根据NT值将242名孕妇分为3组,其中NT2.5~2.9mm组126例,NT3.0~4.5 mm组101例,NT≥4.5 mm组15例;根据产前诊断指标,分成单纯NT增厚组208例和NT增厚合并其他组34例。经羊膜腔穿刺获取胎儿的羊水脱落细胞,同时行染色体核型分析及CNV-Seq检测。结果 242例标本中47例存在染色体异常,阳性率为19.42%,疑似致病或明确致病的有28例,其中2.5~2.9 mm组10例(7.94%),3.0~4.5 mm组14例(13.86%),≥4.5 mm组4例(26.67%);临床意义不明者15例,多态性改变或平衡易位者4例。单纯NT增厚组、NT增厚合并其他组的染色体异常检出率分别为9.62%(20/208)和23.53%(8/34),差异有统计学意义(P=0.019)。结论 NT值增大且合并其他多项指征时,胎儿染色体异常风险增高;染色体核型分析联合CNV-Seq检测,不仅可发现致病性染色体微缺失/微重复,还可明确染色体结构重排病例的异常片段来源,为临床诊断提供更详细、准确的信息,有利于临床进行遗传咨询。

Objective To investigate the genetic etiology of fetus with increased nuchal translucency(NT) and the application of CNV-Seq combined with karyotype analysis.Methods 242 pregnant women with NT≥2.5mm were selected for prenatal diagnosis in Prenatal Diagnosis Center of Maternal and Child Health Care Hospital of Dongchangfu District during January 2017 to April 2022.According to the thickness of NT,the patients were divided into 3 groups: 126 cases in 2.5-2.9mm group, 101 cases in 3.0-4.5mm group and 15 cases in NT≥4.5mm group.According to prenatal diagnostic indexes, 208 cases were divided into NT thickening group and 34 cases in NT thickening combined with other indexes group.Fetal specimen were obtained by amniocentesis, and karyotype analysis combined with CNV-Seq were performed.Results Among the 242 specimens, 47 cases had chromosomal abnormalities, with a positive rate of 19.42%,and 28 cases were suspected or definitely pathogenic, including 10 cases(7.94%) in 2.5-2.9mm group, 14 cases(13.86%) in 3.0-4.5mm group, and 4 cases(26.67%) in ≥4.5mm group.10 cases with unknown clinical significance, and 4 cases with polymorphic change or balanced translocation.There was significant difference in the frequency of chromosome abnormality among NT thickening group(9.62%) and NT thickening combined with other indexes group(23.53%)(P=0.019).Conclusion When NT value increases and other indications are combined, the risk of fetal chromosome abnormality increases;Karyotype analysis combined with CNV-Seq detection can not only find pathogenic chromosome microdeletion/microduplication, but also clarify the source of abnormal fragments in cases of chromosome rearrangement, providing more detailed and accurate information for clinical diagnosis, which is conducive to clinical genetic counseling.