Genetic etiologies associated with infantile hydrocephalus in a Chinese infantile cohort

• Published in: World journal of pediatrics : WJP Vol. 17; no. 3; pp. 305 - 316
• Main Authors: Mei, Hong-Fang, Dong, Xin-Ran, Chen, Hui-Yao, Lu, Yu-Lan, Wu, Bing-Bing, Wang, Hui-Jun, Cheng, Guo-Qiang, Wang, Lai-Shuan, Cao, Yun, Yang, Lin, Zhou, Wen-Hao
• Format: Journal Article
• Language: English
• Published: Singapore Springer Singapore 01.06.2021; Department of Neonatology,Children's Hospital of Fudan University,National Children's Medical Center,Shanghai,China%Key Laboratory of Birth Defects,Children's Hospital of Fudan University,National Children's Medical Center,Shanghai,China%Center for Molecular Medicine of Children's Hospital of Fudan University,Institutes of Biomedical Sciences,Fudan University,Shanghai,China%Clinical Genetic Center,Children's Hospital of Fudan University,National Children's Medical Center,399 Wan Yuan Road,Shanghai 201102,China%Department of Neonatology,Children's Hospital of Fudan University,National Children's Medical Center,Shanghai,China; Key Laboratory of Birth Defects,Children's Hospital of Fudan University,National Children's Medical Center,Shanghai,China; Clinical Genetic Center,Children's Hospital of Fudan University,National Children's Medical Center,399 Wan Yuan Road,Shanghai 201102,China
• Subjects: Critical Care Medicine; Imaging; Intensive; Maternal and Child Health; Medicine; Medicine & Public Health; Original Article; Pediatric Surgery; Pediatrics; Radiology; Surgery; Genetic; Hydrocephalus; Etiology; Infantile
• ISSN: 1708-8569; 1867-0687
• DOI: 10.1007/s12519-021-00429-w

Background Infantile hydrocephalus (IHC) is commonly related to other central nervous system diseases, which may have adverse effects on prognosis. The causes of IHC are heterogeneous, and the genetic etiologies are not fully understood. This study aimed to analyze the genetic etiologies of an IHC cohort. Methods The data for 110 IHC patients who had received exome sequencing at the Clinical Genetic Center of the Children’s Hospital of Fudan University between 2016 and 2019 were reviewed and analyzed retrospectively. An exome-wide association analysis (EWAS) was performed within this cohort using IHC as the study phenotype. Results Of the 110 IHC patients, a pathogenic or likely pathogenic variant was identified in 16 (15%) patients, spanning 13 genes. The genes were mainly associated with metabolic disorders, brain abnormalities, and genetic syndromes. IHC patients who had unclear clinical etiology were more likely to possess a genetic etiology. Based on previous studies and on our EWAS results, ZEB1 , SBF2 , and GNAI2 were over-represented among IHC patients and might affect the signaling pathways involved in IHC formation. Conclusions Our study showed heterogeneous genetic etiologies in an IHC cohort. It is essential to perform genetic testing on IHC patients who have unclear clinical etiology, and genes associated with metabolic disorders, brain abnormalities, and genetic syndromes should be noted. In addition, when aiming to discover IHC susceptibility genes, genes that might influence the signaling pathways involved in IHC formation should be prioritized.