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Comprehensive whole-genome sequence analyses provide insights into the genomic architecture of cerebral palsy.
Fehlings, Darcy L; Zarrei, Mehdi; Engchuan, Worrawat; Sondheimer, Neal; Thiruvahindrapuram, Bhooma; MacDonald, Jeffrey R; Higginbotham, Edward J; Thapa, Ritesh; Behlim, Tarannum; Aimola, Sabrina; Switzer, Lauren; Ng, Pamela; Wei, John; Danthi, Prakroothi S; Pellecchia, Giovanna; Lamoureux, Sylvia; Ho, Karen; Pereira, Sergio L; de Rijke, Jill; Sung, Wilson W L; Mowjoodi, Alireza; Howe, Jennifer L; Nalpathamkalam, Thomas; Manshaei, Roozbeh; Ghaffari, Siavash; Whitney, Joseph; Patel, Rohan V; Hamdan, Omar; Shaath, Rulan; Trost, Brett; Knights, Shannon; Samdup, Dawa; McCormick, Anna; Hunt, Carolyn; Kirton, Adam; Kawamura, Anne; Mesterman, Ronit; Gorter, Jan Willem; Dlamini, Nomazulu; Merico, Daniele; Hilali, Murto; Hirschfeld, Kyle; Grover, Kritika; Bautista, Nelson X; Han, Kara; Marshall, Christian R; Yuen, Ryan K C; Subbarao, Padmaja; Azad, Meghan B; Turvey, Stuart E.
Afiliação
  • Fehlings DL; Division of Developmental Paediatrics, Holland Bloorview Kids Rehabilitation Hospital, Toronto, Ontario, Canada.
  • Zarrei M; Department of Paediatrics, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
  • Engchuan W; The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, Ontario, Canada.
  • Sondheimer N; Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada.
  • Thiruvahindrapuram B; The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, Ontario, Canada.
  • MacDonald JR; Department of Paediatrics, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
  • Higginbotham EJ; Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada.
  • Thapa R; Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
  • Behlim T; The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, Ontario, Canada.
  • Aimola S; The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, Ontario, Canada.
  • Switzer L; Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada.
  • Ng P; The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, Ontario, Canada.
  • Wei J; Genome Diagnostics, Department of Paediatric Laboratory Medicine, The Hospital for Sick Children, Toronto, Ontario, Canada.
  • Danthi PS; Division of Developmental Paediatrics, Holland Bloorview Kids Rehabilitation Hospital, Toronto, Ontario, Canada.
  • Pellecchia G; Centre for Outcomes Research and Evaluation, Research Institute of the McGill University Health Centre, Montréal, Québec, Canada.
  • Lamoureux S; Division of Developmental Paediatrics, Holland Bloorview Kids Rehabilitation Hospital, Toronto, Ontario, Canada.
  • Ho K; Division of Developmental Paediatrics, Holland Bloorview Kids Rehabilitation Hospital, Toronto, Ontario, Canada.
  • Pereira SL; Centre for Outcomes Research and Evaluation, Research Institute of the McGill University Health Centre, Montréal, Québec, Canada.
  • de Rijke J; The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, Ontario, Canada.
  • Sung WWL; The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, Ontario, Canada.
  • Mowjoodi A; The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, Ontario, Canada.
  • Howe JL; The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, Ontario, Canada.
  • Nalpathamkalam T; The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, Ontario, Canada.
  • Manshaei R; The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, Ontario, Canada.
  • Ghaffari S; The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, Ontario, Canada.
  • Whitney J; The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, Ontario, Canada.
  • Patel RV; Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada.
  • Hamdan O; The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, Ontario, Canada.
  • Shaath R; Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada.
  • Trost B; The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, Ontario, Canada.
  • Knights S; The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, Ontario, Canada.
  • Samdup D; The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, Ontario, Canada.
  • McCormick A; Ted Rogers Centre for Heart Research, Cardiac Genome Clinic, The Hospital for Sick Children, Toronto, Ontario, Canada.
  • Hunt C; The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, Ontario, Canada.
  • Kirton A; Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada.
  • Kawamura A; The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, Ontario, Canada.
  • Mesterman R; The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, Ontario, Canada.
  • Gorter JW; The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, Ontario, Canada.
  • Dlamini N; The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, Ontario, Canada.
  • Merico D; The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, Ontario, Canada.
  • Hilali M; Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada.
  • Hirschfeld K; Department of Paediatrics, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
  • Grover K; Grandview Children's Centre, Oshawa, Ontario, Canada.
  • Bautista NX; Department of Pediatrics, Queen's University, Kingston, Ontario, Canada.
  • Han K; Children's Hospital of Eastern Ontario and University of Ottawa, Ottawa, Ontario, Canada.
  • Marshall CR; Grandview Children's Centre, Oshawa, Ontario, Canada.
  • Yuen RKC; Department of Pediatrics, Department of Clinical Neuroscience, University of Calgary, Calgary, Alberta, Canada.
  • Subbarao P; Division of Developmental Paediatrics, Holland Bloorview Kids Rehabilitation Hospital, Toronto, Ontario, Canada.
  • Azad MB; Department of Paediatrics, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
  • Turvey SE; Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada.
Nat Genet ; 56(4): 585-594, 2024 Apr.
Article em En | MEDLINE | ID: mdl-38553553
ABSTRACT
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Paralisia Cerebral / Variações do Número de Cópias de DNA Limite: Child / Humans Idioma: En Revista: Nat Genet Assunto da revista: GENETICA MEDICA Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Canadá País de publicação: Estados Unidos
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Paralisia Cerebral / Variações do Número de Cópias de DNA Limite: Child / Humans Idioma: En Revista: Nat Genet Assunto da revista: GENETICA MEDICA Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Canadá País de publicação: Estados Unidos