染色体微阵列分析在中枢神经系统畸形胎儿诊断中的应用

Clinical application of chromosomal microarray analysis in the diagnosis of fetal central nervous system malformations

目的:评估232例中枢神经系统(CNS)畸形胎儿的染色体变异,并探讨基因型和表型的相关性。方法:通过染色体微阵列分析(CMA)和染色体核型分析,筛选2014年至2022年温州市中心医院产前影像学诊断为CNS畸形的232例胎儿携带的染色体变异,对变异进行致病性评估并分析各类CNS畸形的检出率。结果:染色体核型异常检出率为9.1%(19/209),CMA整体染色体异常检出率为22.8%(53/232),包括多倍体1例(1/232,0.4%),非整倍体19例(19/232,8.2%),其他致病或可能致病的拷贝数变异(CNVs)33例(33/232,14.2%)。CNVs涉及12种微缺失/微重复综合征、14号染色体单亲二体及剂量敏感基因DLL1、FOXC1、SHH、ZIC2、CHAMP1等。非孤立性CNS畸形的致病性变异检出率明显高于孤立性CNS畸形,差异有统计学意义(47.4%vs.14.9%,P<0.01)。结论:CMA是一种快速可靠检出CNS畸形相关CNVs的分子技术,CNS表型和基因型相关性的研究有助于出生缺陷防治和致病机制探索。

Objective:To assess chromosomal variations in 232 fetuses diagnosed with central nervous system(CNS)malformations and explore the relationship between genotype and phenotype.Methods:By chromosomal microarray analysis(CMA)and karyotyping,232 fetuses with CNS malformations diagnosed by prenatal imaging in Wenzhou Central Hospital from 2014 to 2022 were screened for chromosomal variations.The pathogenicity of the detected variations was evaluated and the detection rates across different CNS malformation types was analyzed was analyzed.Results:The results revealed that the detection rate for chromosomal karyotype abnormalities was 9.1%(19/209),while the overall chromosomal abnormality detection rate using CMA was 22.8%(53/232).These abnormalities included one case of polyploidy(1/232,0.4%),19 cases of aneuploidy(19/232,8.2%),and 33 other pathogenic or likely pathogenic copy number variations(CNVs)(33/232,14.2%).The CNVs involved 12 types of microdeletion/microduplication syndromes,uniparental disomy of chromosome 14,and several dosage-sensitive genes,including DLL1,FOXC1,SHH,ZIC2,and CHAMP1.Furthermore,fetuses with non-isolated CNS malformations had a higher rate of pathogenic variations than those with isolated CNS anomalies,and the difference was statistically significant(47.4%vs.14.9%,P<0.01).Conclusion:In conclusion,CMA is a rapid and reliable technique for detecting CNVs associated with CNS malformations.Research on the correlation between CNS phenotype and genotype is vital for the prevention and control of congenital disabilities and pathogenic mechanisms.