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

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. Using exome sequencing data from one of the largest cohorts of children with cerebral palsy, the genetic diagnostic rates of single-nucleotide and copy number variants were assessed and a sizeable fraction found to be clinically actionable.

Xu, Yiran (author)
Zhou, Chongchen (author)
Cheng, Ye (author)
Qiao, Niu (author)
Shang, Qing (author)
Xia, Lei (author)
Song, Juan (author)
Gao, Chao (author)
Qiao, Yimeng (author)
Zhang, Xiaoli (author)
Li, Ming (author)
Ma, Caiyun (author)
Fan, Yangyi (author)
Peng, Xirui (author)
Wu, Silin (author)
Lv, Nan (author)
Li, Bingbing (author)
Sun, Yanyan (author)
Zhang, Bohao (author)
Li, Tongchuan (author)
Li, Hongwei (author)
Zhang, Jin (author)
Su, Yu (author)
Li, Qiaoli (author)
Yuan, Junying (author)
Liu, Lei (author)
Moreno-De-Luca, Andres (author)
Maclennan, Alastair H. (author)
Gecz, Jozef (author)
Zhu, Dengna (author)
Wang, Xiaoyang,1965Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för obstetrik och gynekologi,Institute of Clinical Sciences, Department of Obstetrics and Gynecology(Swepub:gu)xwanxi (author)
Zhu, Changlian (author)
Xing, Qinghe (author)
Göteborgs universitetInstitutionen för kliniska vetenskaper, Avdelningen för obstetrik och gynekologi (creator_code:org_t)

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Medical Genetics

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.