Novel and recurrent variants identified in fetuses with central nervous system abnormalities by trios-medical exome
Hu Tan1, Yinong Xie2, Fei Chen2
1Key Laboratory for Major Obstetric Diseases of Guangdong Province, Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, Guangdong, China; The Medical Centre for Critical Pregnant Women in Guangzhou, Guangzhou 510150, China; Obstetrics & Gynecology Institute of Guangzhou, Guangzhou 510150, China.
Background:
Fetal central nervous system abnormalities often associated with infant death or severe disability. The etiology in fetuses with CNS abnormalities who have normal karyotypes and copy number variants (CNVs) remains unclear, which increases the difficulty in following management and the assessment of prognosis.
Method:
11 unrelated fetuses with CNS abnormalities and their parents were enrolled. Genomic DNA was obtained and then trios-medical exome sequencing (trios-MES) including 4000 genes (fetuses and their parents) was performed after both karyotyping and chromosome microarray showed negative results.
Results:
Pathogenic and likely pathogenic variants were identified in five of 11 cases (5/11, 45.5%), including five novel mutations and two recurrent mutations in ISPD, L1CAM, and GRIN2B genes. Most cases (4/5, 80%) carried one or two recessive mutations, indicating a high recurrent risk.
Conclusion:
Exome sequencing should be considered for fetuses with CNS abnormalities following negative results of karyotyping and chromosome array. Trios-MES as one of exome sequencing is a potential method for the diagnosis of these fetuses.
