Xue Huili, Yu Aili, Zheng Lin, Ye Xianglan, Zhang Lin, Guo Qun, Chen Lingji, Shen Qingmei, Lin Na, Huang Hailong, Xu Liangpu
Medical Genetic Diagnosis and Therapy Center, Fujian Key Laboratory for Prenatal Diagnosis and Birth Defect, Fujian Maternity and Child Health Hospital College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, No. 18 Daoshan Road, Gulou District, Fuzhou, 350001, Fujian Province, China.
Reproductive Medicine Center, Fujian Maternity and Child Health Hospital College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, No. 18 Daoshan Road, Gulou District, Fuzhou, 350001, Fujian Province, China.
Sci Rep. 2025 Jul 1;15(1):20634. doi: 10.1038/s41598-025-07105-3.
To evaluate the clinical utility of genetic testing via karyotyping, chromosomal microarray analysis (CMA), and exome sequencing in cases with corpus callosum abnormalities (CCA). Here, 65 prenatal and 12 postnatal cases diagnosed with CCA via ultrasound and magnetic resonance imaging examination were enrolled. All cases were divided into two groups: 21 (27.3%) isolated and 56 (72.7%) non-isolated CCA groups. Karyotyping and CMA were first performed in parallel, then followed by whole exome sequencing (WES) after negative karyotype and CMA results. Clinical outcomes were also followed up. Karyotype abnormalities were identified in 7 cases (9.1%, 7/77). Karyotype abnormality rates in the isolated and non-isolated CCA groups were 8.0% and 9.6%, respectively (p > 0.05). Pathogenic/likely pathogenic (P/LP) CNVs were identified in 11 cases (14.3%, 11/77), including 2(9.5%, 2/21) and 9(16.1%, 9/56) cases in the isolated and non-isolated CCA groups, respectively (p > 0.05). WES identified P/LP diagnostic genetic variants in 8 (47.1%, 8/17) cases, including 2 and 6 cases in the isolated and non-isolated CCA groups, respectively. Additionally, 3 cases with variants of unknown significance were identified. Of the 65 prenatal cases with CCA, 31 (47.7%) were terminated, 1 (1.5%) was a miscarriage, 33 (50.8%) yielded live born babies; of these, 4(12.1%, 4/33) yielded babies with neurodevelopment disorders (NDDs). Of the 12 postnatal cases with CCA, all presented NDDs. Genetic causes of CCA are highly variable. Prenatal brain magnetic resonance imaging and systemic ultrasound examination should be performed to examine other anomalies when CCAs are detected via ultrasound. WES is also recommended following negative karyotype and CMA results.
评估核型分析、染色体微阵列分析（CMA）和外显子组测序在胼胝体异常（CCA）病例中的临床应用价值。本研究纳入了65例产前和12例产后经超声和磁共振成像检查诊断为CCA的病例。所有病例分为两组：21例（27.3%）孤立性CCA组和56例（72.7%）非孤立性CCA组。首先并行进行核型分析和CMA，核型和CMA结果为阴性后再进行全外显子组测序（WES）。同时对临床结局进行随访。7例（9.1%，7/77）检测到核型异常。孤立性和非孤立性CCA组的核型异常率分别为8.0%和9.6%（p＞0.05）。11例（14.3%，11/77）检测到致病性/可能致病性（P/LP）拷贝数变异（CNV），其中孤立性和非孤立性CCA组分别为2例（9.5%，2/21）和9例（16.1%，9/56）（p＞0.05）。WES在8例（47.1%，8/17）病例中检测到P/LP诊断性基因变异，其中孤立性和非孤立性CCA组分别为2例和6例。此外，还检测到3例意义未明的变异。65例产前CCA病例中，31例（47.7%）终止妊娠，1例（1.5%）流产，33例（50.8%）分娩活婴；其中4例（12.1%，4/33）婴儿患有神经发育障碍（NDD）。12例产后CCA病例均患有NDD。CCA的遗传原因高度可变。当通过超声检测到CCA时，应进行产前脑磁共振成像和全身超声检查以排查其他异常。核型和CMA结果为阴性后也建议进行WES。
