染色体微阵列分析在持续性左上腔静脉胎儿中的临床应用

Fetal Persistent Left Superior Vena Cava Associated with Abnormal Karyotypes and Copy Number Variations

【目的】探讨染色体微阵列分析技术(CMA)在全基因组水平分析持续性左上腔静脉(PLSVC)胎儿遗传性病因的临床应用价值。【方法】2014年1月至2016年12月在中山大学附属第一医院行胎儿系统超声筛查提示持续性左上腔静脉且在我院产前诊断中心接受常规染色体核型分析和CMA检测的81例胎儿纳入研究,比较持续性左上腔静脉胎儿核型分析和CMA检测染色体异常的检出率差异。根据是否合并其他超声异常,分为单纯组及合并异常组,比较单纯组与合并异常组染色体异常检出率差异。【结果】核型分析的异常率为18.5%(15/81),CMA的异常检出率为23.5%(19/81);两种检测方法染色体异常的检出率比较,差异无统计学意义(P=0.44)。CMA在核型正常的持续性左上腔静脉胎儿中,额外检出6.1%(4/66)具有临床意义的染色体微缺失或微重复,且均合并其他异常。单纯组12例(14.8%,12/81),合并异常组69例(85.2%,69/81)。两组间染色体异常的检出率差异无统计学意义(26.1%,18/69 vs. 8.3%,1/12,P=0.277)。合并异常组中房室间隔缺损、颜面部异常,以及多发超声软指标异常在染色体异常胎儿中的检出率显著高于染色体正常胎儿(P=0.030,P=0.012,P=0.014)。【结论】在持续性左上腔静脉胎儿中,特别是合并其他超声异常时,染色体微阵列分析可检测出传统核型分析无法检出的染色体微缺失/微重复,对产前诊断及遗传学咨询具有重要价值。

【Objective】To investigate the clinical value of chromosomal microarray analysis(CMA)for fetuses with persistent left superior vena cava(PLSVC).【Methods】Fetuses that were diagnosed with PLSVC during ultrasound examination and underwent invasive prenatal testing(on which karyotyping and CMA were both performed)from January 2014 to December 2016 at the First Affiliated Hospital of Sun Yat-sen University were reviewed. According to the combination of other ultrasound abnormalities,the cases were divided into isolated group and complicated group.【Results】Karyotype analysis identified chromosomal aberrations in 18.5%(15/81)of the fetuses,while CMA detected pathogenic copy number variations(CNV)in 23.5%(19/81)of the fetuses. There was no significant difference in the detection rate of chromosomal abnormalities between the Karyotype analysis and CMA(P = 0.44). CMA achieved an incremental yield of 6.1%(4/66)among PLSVC fetuses with normal karyotypes,and only in the complicated cases. There were 12 cases(14.8%,12/81)in isolated group and 69 cases(85.2%,69/81)in complicated group. The frequency of genetic anomalies in the complicated group was not significantly higher than that in the isolated group(26.1%,18/69 vs. 8.3%,1/12,P = 0.277).The incidences of atrioventricular septal defect,facial abnormalities,and multiple soft markers were significantly higher among fetuses with abnormal genetic test results(P = 0.030,P = 0.012,P = 0.014).【Conclusion】CMA is a valuable tool for identifying additional unbalanced submicroscopic chromosomal abnormalities in fetuses with PLSVC,especially when PLSVC is accompanied by other ultrasound malformations.