G显带和多重连接依赖探针扩增联合分析心脏发育畸形胎儿的染色体异常

Combined G-banded karyotyping and multiplex ligation-dependent probe amplification for the detection of chromosomal abnormalities in fetuses with congenital heart defects

目的探讨联合应用染色体G显带核型分析与多重连接依赖探针扩增技术（multiplex ligation-dependent probe amplification，MLPA）在检测先天性心脏畸形胎儿的染色体异常中的应用价值。方法应用染色体核型分析联合MLPA技术对104例中孕期B超提示先天性心脏畸形胎儿进行染色体数目和结构异常检测。对检出的染色体异常，进一步通过染色体微阵列分析（chromosomal microarray analysis，CMA）予以验证。结果染色体G显带核型分析与MLPA检测结果显示，在104例先天性心脏畸形胎儿羊水标本中，检出19例染色体异常，异常检出率为18％。93例心脏畸形胎儿的羊水标本进行CMA检测，共检出14例染色体异常，其中10例异常为已知的致病性拷贝数变异（copy number variation，CNV），4例为临床意义未明的CNV。10例致病性CNV羊水标本的MLPA检测结果也显示相同的染色体异常，4例临床意义未明CNV的羊水标本的MLPA检测结果仅1例检出异常。结论染色体G显带核型分析联合MLPA技术是一种快速、经济、有效的检测先天性心脏畸形胎儿染色体异常的方法。

Objective To assess the value of G-banded karyotyping in combination with multiplex ligation-dependent probe amplification （MLPA） as a tool for the detection of chromosomal abnormalities in fetuses with congenital heart defects. Methods The combined method was used to analyze 104 fetuses with heart malformations identified by ultrasonography. Abnormal findings were confirmed with chromosomal microarray analysis （CMA）. Results Nineteen （18%） fetuses were found to harbor chromosomal aberrations by G-banded karyotyping and MLPA. For 93 cases, CMA has detected abnormalities in 14 cases including 10 pathogenic copy number variations （CNVs） and 4 CNVs of uncertain significance （VOUS）. MLPA was able to detect all of the pathogenic CNVs and 1 VOUS CNV. Conclusion Combined use of G- banded karyotyping and MLPA is a rapid, low-cost and effective method to detect chromosomal abnormalities in fetuses with various heart malformations.