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
Children's Hospital of Fudan University and Institutes of Biomedical Sciences of Fudan University, Shanghai, China.
Department of Pediatrics, Henan Key Laboratory of Child Brain Injury and Henan Pediatric Clinical Research Center, The Third Affiliated Hospital and Institute of Neuroscience of Zhengzhou University, Zhengzhou, China.
Nat Med. 2024 May;30(5):1395-1405. doi: 10.1038/s41591-024-02912-z. Epub 2024 May 1.
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.
脑瘫（CP）是儿童中最常见的运动障碍。为了确定主要基因变异在脑瘫病因中的作用，我们对具有脑瘫临床表现的大规模队列进行了外显子组测序。研究队列包括505名女孩和1073名男孩。利用当前基因诊断的金标准，这1578名儿童中有387名（24.5%）获得了基因诊断。我们在与神经发育障碍相关的219个基因中鉴定出412个致病和可能致病（P/LP）变异，以及59个P/LP拷贝数变异。出生时被标记为围产期窒息的脑瘫儿童的基因诊断率高于无窒息儿童（P = 0.0033）。此外，33名有脑瘫表现的儿童（8.5%，387名中的33名）有临床上可采取行动的发现。这些结果凸显了对脑瘫儿童，尤其是有围产期窒息等风险因素的儿童进行早期基因检测的必要性，以便做出基于证据的医疗决策。
