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

目的：总结染色体核型分析联合拷贝数变异测序（copy number variation sequencing,CNV-seq）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≥2.5 mm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。

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

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 pCNVs and chromosome aneuploidy in the non-simple 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 pCNVs (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 pCNVs 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.