Hu Tan1, Yinong Xie2, Fei Chen2, Min Chen2, Li Yu3, Dunjin Chen4, Jingsi Chen5. 1. Key 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. 2. Department of Fetal Medicine and Prenatal Diagnosis, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, China. 3. Key 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. 4. Key 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. Electronic address: chendunjin@hotmail.com. 5. Key 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; Department of Fetal Medicine and Prenatal Diagnosis, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, China; The Medical Centre for Critical Pregnant Women in Guangzhou, Guangzhou 510150, China; Obstetrics & Gynecology Institute of Guangzhou, Guangzhou 510150, China. Electronic address: ceasaw_chen@hotmail.com.
Abstract
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.
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.
Authors: Maayke A de Koning; Mariëtte J V Hoffer; Esther A R Nibbeling; Emilia K Bijlsma; Menno J P Toirkens; Phebe N Adama-Scheltema; E Joanne Verweij; Marieke B Veenhof; Gijs W E Santen; Cacha M P C D Peeters-Scholte Journal: Clin Genet Date: 2021-10-19 Impact factor: 4.296
Authors: Y Yaron; V Ofen Glassner; A Mory; N Zunz Henig; A Kurolap; A Bar Shira; D Brabbing Goldstein; D Marom; L Ben Sira; H Baris Feldman; G Malinger; K Krajden Haratz; A Reches Journal: Ultrasound Obstet Gynecol Date: 2022-07 Impact factor: 8.678