染色体微阵列分析在中枢神经系统异常胎儿产前诊断中的研究

Study on chromosome microarray analysis in prenatal diagnosis of abnormal central nervous system

目的应用染色体微阵列分析技术(chromosomal microarray analysis,CMA)在全基因组水平分析中枢神经系统(Central nervous system,CNS)异常胎儿的遗传学病因。方法对3850例孕妇进行产前诊断,发现中枢神经系统超声异常胎儿12例,并进行胎儿染色体核型分析及全基因组拷贝数变异(copy number variation,CNVs)筛查,筛检有无CNV。针对发现的CNV,通过比对国际基因组CNV多态性数据库排除良性CNV,结合基因组异常拷贝数变异数据库及相关文献,判断CNV的临床意义。结果 12例中枢神经系统异常胎儿中共检出8例CMA异常,其中携带有10个临床致病性CNV,2个临床意义不明确CNV,检出率为66.7%;2例为18三体综合征,其余临床致病性CNV涉及2号、6号、7号、9号、16号、22号及性染色体的拷贝数缺失或重复。结论拷贝数变异是导致胎儿中枢神经系统异常的一个重要遗传学病因,SNP-array技术可作为中枢神经系统异常胎儿产前诊断的一线检测方法。

Objective:The chromosomal microarray analysis(CMA)was used to analyze the genetic cause of abnormal fetal in the central nervous system(CNS)at the genome-wide level. Methods:Prenatal diagnosis was performed on 3850 pregnant women,and 12 cases of abnormal ultrasound in the central nervous system were found. Fetal karyotype analysis and whole-genome copy number variation(CNVs)screening were performed to screen for CNV. For the discovered CNV,the clinical significance of CNV was judged by comparing the benign CNV with the international genomic CNV polymorphism database,combining the genomic abnormal copy number variation database and related literature. Results:Twelve cases of central nervous system abnormalities were detected in 8 cases of CMA abnormalities,including 10 clinically pathogenic CNV,2 clinically unclear CNV,the detection rate was 66.7%;2 cases were 18 trisomy syndrome,The remaining clinically pathogenic CNV involved deletions or duplications in copy number 2,6,7,9,16,22 and sex chromosomes. Conclusions:Copy number variation is an important genetic cause of fetal central nervous system abnormalities. SNP-array technology can be used as a first-line detection method for prenatal diagnosis of central nervous system abnormalities.