染色体核型分析联合CNV-seq在NT增厚胎儿产前诊断中的应用

Application of Chromosome Karyotype Analysis and CNV-Seq in Fetals with Increased Nuchal Translucency

目的:总结染色体核型分析联合拷贝数变异测序(copy number variation sequencing,CNVseq)在颈项透明层(nuchal translucency,NT)增厚胎儿中的应用经验。方法:对189例孕11~13+6周胎儿NT≥2.5mm的单胎胎儿行染色体核型分析及CNV-seq,并对染色体异常检出率进行分析。根据介入产前诊断指征分为单纯NT增厚组(119例)和非单纯NT增厚组(70例),根据NT厚度分为2.5 mm≤NT<3.5 mm组(123例)和NT≥3.5 mm组(66例)。结果:染色体核型分析检出31例(16.40%)染色体异常,包括非整倍体24例(12.70%)和结构异常7例(3.70%)。CNV-seq检出38例(20.11%)致病性拷贝数变异(pathogenic copy number variations,pCNVs),包括非整倍体24例(12.70%)和其他pCNVs 14例(7.41%)。染色体核型正常的胎儿中CNV-seq额外检出9例(5.70%)pCNVs。非单纯NT增厚组pCNVs、染色体非整倍体检出率均高于单纯NT增厚组,差异有统计学意义(P<0.05),其他pCNVs检出率差异无统计学意义(P>0.05)。NT≥3.5 mm组pCNVs、染色体非整倍体检出率均高于2.5 mm≤NT<3.5 mm组,差异有统计学意义(P<0.05),其他pCNVs检出率差异无统计学意义(P>0.05)。结论:随着NT增厚或合并其他介入产前诊断指征的胎儿染色体异常风险增加,但与其他pCNVs无明显相关;CNV-seq联合染色体核型分析有助于检出不同类型的染色体异常,避免染色体结构异常及染色体微缺失/微重复的漏诊。

Objective: To summarize the application of chromosome karyotype analysis combined with copy number variation sequencing(CNV-seq) in the fetuses with increased nuchal translucency(NT). Methods: Karyotype analysis and CNV-seq were performed in 189 singleton fetuses with NT≥2.5 mm and gestation weeks from 11 to 13+6, and the detection rate of chromosomal abnormalities was analyzed. According to the pre-interventional diagnosis indications, they were divided into the simple NT thickening group( n=119) and the non-simple NT thickening group(n=70). According to the NT thickness, they were divided into the 2.5 mm≤NT<3.5 mm group(n=123) and the NT≥3.5 mm group(n=66). Results: Karyotype analysis revealed 31 cases(16.40%) of chromosome abnormalities, including 24 cases(12.70%) of aneuploidy and 7 cases(3.70%) of structural abnormalities, and CNV-seq revealed 38 cases(20.11%) of pathogenic copy number variations(pCNVs), including 24 cases(12.70%)of aneuploidy and 14 cases(7.41%) of other pCNVs. Nine additional cases(5.70%) of pCNVs were detected by CNV-seq in fetuses with normal karyotype. The detection rates of p CNVs and chromosome aneuploidy in the nonsimple NT thickening group were higher than those in the simple NT thickening group, and the differences were statistically significant(P<0.05). There was no significant difference in the detection rates of other p CNVs(P>0.05).The detection rates of pCNVs and chromosome aneuploidy in the NT≥3.5 mm group were higher than those in the 2.5 mm≤NT<3.5 mm group, the differences were statistically significant(P<0.05). There was no significant difference in the other p CNVs detection rates(P> 0.05). Conclusions: Fetal chromosomal abnormalities were increased with NT thickening or other pre-interventional diagnostic indicators, but they were not significantly associated with other pCNVs. CNV-seq combined karyotype analysis can help to detect the different types of chromosomal abnormalities, to avoid the missed diagnosis of chromosomal structural abnormalities and chromosomal microdeletion/microduplication.