학술논문
Exome sequencing reveals genetic heterogeneity and clinically actionable findings in children with cerebral palsy
Document Type
Article
Author
Wang, Yangong; Xu, Yiran; Zhou, Chongchen; Cheng, Ye; Qiao, Niu; Shang, Qing; Xia, Lei; Song, Juan; Gao, Chao; Qiao, Yimeng; Zhang, Xiaoli; Li, Ming; Ma, Caiyun; Fan, Yangyi; Peng, Xirui; Wu, Silin; Lv, Nan; Li, Bingbing; Sun, Yanyan; Zhang, Bohao; Li, Tongchuan; Li, Hongwei; Zhang, Jin; Su, Yu; Li, Qiaoli; Yuan, Junying; Liu, Lei; Moreno-De-Luca, Andres; MacLennan, Alastair H.; Gecz, Jozef; Zhu, Dengna; Wang, Xiaoyang; Zhu, Changlian; Xing, Qinghe
Source
Nature Medicine; 20240101, Issue: Preprints p1-11, 11p
Subject
Language
ISSN
10788956; 1546170X
Abstract
Cerebral palsy (CP) is the most common motor disability in children. To ascertain the role of major genetic variants in the etiology of CP, we conducted exome sequencing on a large-scale cohort with clinical manifestations of CP. The study cohort comprised 505 girls and 1,073 boys. Utilizing the current gold standard in genetic diagnostics, 387 of these 1,578 children (24.5%) received genetic diagnoses. We identified 412 pathogenic and likely pathogenic (P/LP) variants across 219 genes associated with neurodevelopmental disorders, and 59 P/LP copy number variants. The genetic diagnostic rate of children with CP labeled at birth with perinatal asphyxia was higher than the rate in children without asphyxia (P= 0.0033). Also, 33 children with CP manifestations (8.5%, 33 of 387) had findings that were clinically actionable. These results highlight the need for early genetic testing in children with CP, especially those with risk factors like perinatal asphyxia, to enable evidence-based medical decision-making.