Objective: To explore the application value of chromosome karyotype analysis, chromosomal microarray analysis (CMA) and whole exome sequencing (WES) in prenatal diagnosis of isolated corpus callosum abnormality (CCA) fetus. Methods: Fetuses diagnosed with isolated CCA by ultrasound and MRI and receiving invasive prenatal diagnosis in Guangzhou Women and Children's Medical Center and Qingyuan People's Hospital from January 2010 to April 2021 were selected. Karyotype analysis and/or CMA [or copy number variation sequencing (CNV-seq)] were performed on all fetal samples, and WES was performed on fetal samples and their parents whose karyotype analysis and/or CMA (or CNV-seq) results were not abnormal. Results: Among 65 fetuses with isolated CCA, 38 cases underwent karyotype analysis, and 3 cases were detected with abnormal karyotypes, with a detection rate of 8% (3/38). A total of 49 fetuses with isolated CCA underwent CMA (or CNV-seq) detection, and 6 cases of pathogenic CNV were detected, the detection rate was 12% (6/49). Among them, the karyotype analysis results were abnormal, and the detection rate of further CMA detection was 1/1. The karyotype results were normal, and the detection rate of further CMA (or CNV-seq) detection was 14% (3/21). The detection rate of CMA as the first-line detection technique was 7% (2/27). A total of 25 fetuses with isolated CCA with negative results of karyotyping and/or CMA were tested by WES, and 9 cases (36%, 9/25) were detected with pathogenic genes. The gradient genetic diagnosis of chromosomal karyotyping, CMA and WES resulted in a definite genetic diagnosis of 26% (17/65) of isolated CCA fetuses. Conclusions: Prenatal genetic diagnosis of isolated CCA fetuses is of great clinical significance. The detection rate of CMA is higher than that of traditional karyotyping. CMA detection could be used as a first-line detection technique for fetuses with isolated CCA. WES could increase the pathogenicity detection rate of fetuses with isolated CCA when karyotype analysis and/or CMA test results are negative.
目的： 从细胞遗传学、基因组及单基因水平探讨染色体核型分析、染色体微阵列分析（CMA）及全外显子测序（WES）技术在孤立性胼胝体发育异常（CCA）胎儿产前诊断中的应用价值。 方法： 选取2010年1月至2021年4月在广州市妇女儿童医疗中心及清远市人民医院产前诊断中心就诊，超声及MRI检查诊断为孤立性CCA并行侵入性产前诊断的胎儿。对所有胎儿样本行染色体核型分析和（或）CMA［或拷贝数变异测序（CNV-seq）］检测，对染色体核型分析和（或）CMA（或CNV-seq）检测结果未见异常的胎儿及其父母样本进一步行WES检测。 结果： 65例孤立性CCA胎儿中，行染色体核型分析38例，检出异常染色体核型3例，检出率为8%（3/38）。共计49例孤立性CCA胎儿行CMA（或CNV-seq）检测，检出致病性CNV 6例，检出率为12%（6/49），其中，染色体核型分析结果异常，进一步行CMA检测的检出率为1/1；染色体核型结果正常，进一步行CMA（或CNV-seq）检测的检出率为14%（3/21）；以CMA检测为一线检测技术的检出率为7%（2/27）。共计25例染色体核型分析和（或）CMA检测结果阴性的孤立性CCA胎儿行WES检测，检出致病基因9例，检出率为36%（9/25）。染色体核型分析、CMA及WES三种检测技术的梯度遗传学诊断使26%（17/65）孤立性CCA胎儿得到明确的遗传学诊断。 结论： 对孤立性CCA胎儿进行产前遗传学诊断具有重要的临床意义，CMA检测的检出率高于传统的染色体核型分析技术。CMA检测可作为孤立性CCA胎儿的一线检测技术，染色体核型分析和（或）CMA检测结果阴性时，WES可额外提高孤立性CCA胎儿的致病性检出率。.