Exome sequencing reveals genetic heterogeneity and clinically actionable findings in children with cerebral palsy

被引：6

作者：

Wang, Yangong ^{[1
,2
]}

Xu, Yiran ^{[3
,4
,5
]}

Zhou, Chongchen ^{[6
]}

Cheng, Ye ^{[1
,2
,7
]}

Qiao, Niu ^{[8
,9
]}

Shang, Qing ^{[6
]}

Xia, Lei ^{[3
,4
,5
]}

Song, Juan ^{[3
,4
,5
]}

Gao, Chao ^{[6
]}

Qiao, Yimeng ^{[1
,2
,3
,4
,5
]}

Zhang, Xiaoli ^{[3
,4
,5
]}

Li, Ming ^{[3
,4
,5
]}

Ma, Caiyun ^{[6
]}

Fan, Yangyi ^{[1
,2
]}

Peng, Xirui ^{[3
,4
,5
]}

Wu, Silin ^{[10
]}

Lv, Nan ^{[6
]}

Li, Bingbing ^{[3
,4
,5
]}

Sun, Yanyan ^{[3
,4
,5
]}

Zhang, Bohao ^{[3
,4
,5
]}

Li, Tongchuan ^{[3
,4
,5
]}

Li, Hongwei ^{[3
,4
,5
]}

Zhang, Jin ^{[1
,2
,7
]}

Su, Yu ^{[1
,2
]}

Li, Qiaoli ^{[1
,2
]}

Yuan, Junying ^{[3
,4
,5
]}

Liu, Lei ^{[1
,2
]}

Moreno-De-Luca, Andres ^{[11
]}

MacLennan, Alastair H. ^{[12
,13
]}

Gecz, Jozef ^{[12
,13
]}

Zhu, Dengna ^{[3
,4
,5
]}

Wang, Xiaoyang ^{[14
]}

Zhu, Changlian ^{[3
,4
,5
]}

Xing, Qinghe ^{[1
,2
,7
]}

机构：

[1] Fudan Univ, Childrens Hosp, Shanghai, Peoples R China

[2] Fudan Univ, Inst Biomed Sci, Shanghai, Peoples R China

[3] Zhengzhou Univ, Dept Pediat, Henan Key Lab Child Brain Injury, Zhengzhou, Peoples R China

[4] Zhengzhou Univ, Henan Pediat Clin Res Ctr, Affiliated Hosp 3, Zhengzhou, Peoples R China

[5] Zhengzhou Univ, Inst Neurosci, Zhengzhou, Peoples R China

[6] Zhengzhou Univ, Rehabil Dept, Henan Key Lab Child Genet & Metab, Childrens Hosp, Zhengzhou, Peoples R China

[7] Shanghai Ctr Women & Childrens Hlth, Shanghai, Peoples R China

[8] Shanghai Jiao Tong Univ, Shanghai Inst Hematol, State Key Lab Med Genom, Natl Res Ctr Translat Med Shanghai, Shanghai, Peoples R China

[9] Shanghai Jiao Tong Univ, Sch Life Sci & Biotechnol, Shanghai, Peoples R China

[10] Fudan Univ, Dept Neurosurg, Affiliated Zhongshan Hosp, Shanghai, Peoples R China

[11] Queens Univ, Kingston Hlth Sci Ctr, Neuroradiol Sect, Fac Hlth Sci,Dept Radiol, Kingston, ON, Canada

[12] Univ Adelaide, Robinson Res Inst, Adelaide, SA, Australia

[13] Univ Adelaide, Adelaide Med Sch, Adelaide, SA, Australia

[14] Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Ctr Perinatal Med & Hlth, Gothenburg, Sweden

来源：

NATURE MEDICINE | 2024年 / 30卷 / 05期

基金：

瑞典研究理事会; 中国国家自然科学基金;

关键词：

INTELLECTUAL DISABILITY; DEFICIENCY CAUSES; BIRTH ASPHYXIA; CLASSIFICATION; PREVALENCE; HYPOTHERMIA; MUTATIONS; DOPA;

D O I：

10.1038/s41591-024-02912-z

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 59P/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.

引用

页码：1395 / +

页数：23

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