Comprehensive whole-genome sequence analyses provide insights into the genomic architecture of cerebral palsy.
Journal
Nature genetics
ISSN: 1546-1718
Titre abrégé: Nat Genet
Pays: United States
ID NLM: 9216904
Informations de publication
Date de publication:
29 Mar 2024
29 Mar 2024
Historique:
received:
23
12
2022
accepted:
13
02
2024
medline:
30
3
2024
pubmed:
30
3
2024
entrez:
30
3
2024
Statut:
aheadofprint
Résumé
We performed whole-genome sequencing (WGS) in 327 children with cerebral palsy (CP) and their biological parents. We classified 37 of 327 (11.3%) children as having pathogenic/likely pathogenic (P/LP) variants and 58 of 327 (17.7%) as having variants of uncertain significance. Multiple classes of P/LP variants included single-nucleotide variants (SNVs)/indels (6.7%), copy number variations (3.4%) and mitochondrial mutations (1.5%). The COL4A1 gene had the most P/LP SNVs. We also analyzed two pediatric control cohorts (n = 203 trios and n = 89 sib-pair families) to provide a baseline for de novo mutation rates and genetic burden analyses, the latter of which demonstrated associations between de novo deleterious variants and genes related to the nervous system. An enrichment analysis revealed previously undescribed plausible candidate CP genes (SMOC1, KDM5B, BCL11A and CYP51A1). A multifactorial CP risk profile and substantial presence of P/LP variants combine to support WGS in the diagnostic work-up across all CP and related phenotypes.
Identifiants
pubmed: 38553553
doi: 10.1038/s41588-024-01686-x
pii: 10.1038/s41588-024-01686-x
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Ontario Brain Institute (Institut Ontarien du Cerveau)
ID : Childhood Cerebral Palsy Neuroscience Discovery Network (CP-NET)
Organisme : Ontario Brain Institute (Institut Ontarien du Cerveau)
ID : Childhood Cerebral Palsy Neuroscience Discovery Network (CP-NET)
Organisme : Gouvernement du Canada | Canadian Institutes of Health Research (Instituts de Recherche en Santé du Canada)
ID : PJT-153004
Organisme : Gouvernement du Canada | Canadian Institutes of Health Research (Instituts de Recherche en Santé du Canada)
ID : PJT-153004
Organisme : Gouvernement du Canada | Canadian Institutes of Health Research (Instituts de Recherche en Santé du Canada)
ID : PJT-175329
Organisme : Gouvernement du Canada | Canadian Institutes of Health Research (Instituts de Recherche en Santé du Canada)
ID : PJT-153004
Informations de copyright
© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.
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