Chromosome karyotype analysis,copy number variation sequencing and whole exome sequencing in prenatal diagnosis of fetuses with corpus callosum anomalies
Objective To investigate the application values of chromosome karyotype analysis,copy number variation sequencing(CNV-seq)and whole exome sequencing(WES)to the prenatal diagnosis of fetuses with corpus callosum anomalies(CCA).Methods Thirty-nine fetuses were diagnosed with CCA by ultrasound and/or MRI in the First Affiliated Hospital of Zhengzhou University from July 2015 and December 2023,and the brain and other extracranial anomalies were observed.The amniotic fluid samples were collected to perform karyotype analysis in 14 fetuses and CNV-seq in 39.In 34 variants of uncertain significance and normal fetuses from karyotype analysis and CNV-seq,6 fetuses were performed trio-WES.All 39 fetuses with CCA were followed up till 6 to 12 months after birth to record the pregnancy outcomes.Results Among 39 CCA fetuses,there were 2 cases of complete agenesis,15 cases of partial agenesis,and 22 cases of dysgenesis of the corpus callosum;13 were isolated CCA,and 26 were complex CCA.The most common co-occurring anomalies were brain abnormalities,including 13 cases of enlarged lateral ventricles and 14 cases of cavum septipellucidi anomalies.The karyotype analysis results of 14 fetuses with CCA identified 1 case(7.1％)of trisomy 21,and 13 cases of normal karyotype.CNV-seq results of 39 fetuses confirmed CCA-related pathogenic CNVs in 4 cases(10.3％),2 cases of variants of uncertain significance CNV,and 33 cases of normal CNV.Trio-WES results of 6 cases identified CCA-related pathogenic mutations in 2 cases(33.3％).The follow-up results showed that among these 13 isolated CCA cases,there were 9 of born alive and 1 of induced abortion,and 3 were lost to follow up;among these 26 complex CCA cases,there were 2 of born alive and 12 of induced abortion,and 12 were lost to follow up.There was 1 case of chromosomal karyotype abnormality,2 cases of pathogenic CNVs,1 case of variants of uncertain signicance CNV and 2 fetuses of pathogenic mutations detected by trio-WES who were performed induced abortion;among 4 cases with negative trio-WES,3 were born alive,and 1 was performed induced abortion.Conclusions CNV-seq can be used as a first-line detection technique to screen genetic causes for CCA fetuses diagnosed by ultrasound or MRI.For those with variants of uncertain significance and normal fetuses from CNV-seq,trio-WES is suggested,and it can improve the detection rate of pathogenic mutation of CCA fetuses and contributes to pregnancy decision-making and fetal development prediction after birth.
corpus callosum anomalieswhole exome sequencingcopy number variation sequencingchromosome karyotype analysisfetus
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