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Post-zygotic rescue of meiotic errors causes brain mosaicism and focal epilepsy.
Miller, Katherine E; Rivaldi, Adithe C; Shinagawa, Noriyuki; Sran, Sahib; Navarro, Jason B; Westfall, Jesse J; Miller, Anthony R; Roberts, Ryan D; Akkari, Yassmine; Supinger, Rachel; Hester, Mark E; Marhabaie, Mohammad; Gade, Meethila; Lu, Jinfeng; Rodziyevska, Olga; Bhattacharjee, Meenakshi B; Von Allmen, Gretchen K; Yang, Edward; Lidov, Hart G W; Harini, Chellamani; Shah, Manish N; Leonard, Jeffrey; Pindrik, Jonathan; Shaikhouni, Ammar; Goldman, James E; Pierson, Christopher R; Thomas, Diana L; Boué, Daniel R; Ostendorf, Adam P; Mardis, Elaine R; Poduri, Annapurna; Koboldt, Daniel C; Heinzen, Erin L; Bedrosian, Tracy A.
Afiliación
  • Miller KE; Institute for Genomic Medicine, Nationwide Children's Hospital, Columbus, OH, USA.
  • Rivaldi AC; Department of Pediatrics, The Ohio State University, Columbus, OH, USA.
  • Shinagawa N; Institute for Genomic Medicine, Nationwide Children's Hospital, Columbus, OH, USA.
  • Sran S; Institute for Genomic Medicine, Nationwide Children's Hospital, Columbus, OH, USA.
  • Navarro JB; Institute for Genomic Medicine, Nationwide Children's Hospital, Columbus, OH, USA.
  • Westfall JJ; Institute for Genomic Medicine, Nationwide Children's Hospital, Columbus, OH, USA.
  • Miller AR; Institute for Genomic Medicine, Nationwide Children's Hospital, Columbus, OH, USA.
  • Roberts RD; Institute for Genomic Medicine, Nationwide Children's Hospital, Columbus, OH, USA.
  • Akkari Y; Department of Pediatrics, The Ohio State University, Columbus, OH, USA.
  • Supinger R; Institute for Genomic Medicine, Nationwide Children's Hospital, Columbus, OH, USA.
  • Hester ME; Institute for Genomic Medicine, Nationwide Children's Hospital, Columbus, OH, USA.
  • Marhabaie M; Institute for Genomic Medicine, Nationwide Children's Hospital, Columbus, OH, USA.
  • Gade M; Department of Pediatrics, The Ohio State University, Columbus, OH, USA.
  • Lu J; Institute for Genomic Medicine, Nationwide Children's Hospital, Columbus, OH, USA.
  • Rodziyevska O; Division of Pharmacotherapy and Experimental Therapeutics in the Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Bhattacharjee MB; Division of Pharmacotherapy and Experimental Therapeutics in the Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Von Allmen GK; Division of Child Neurology, Department of Pediatrics, McGovern Medical School, Houston, TX, USA.
  • Yang E; Department of Pathology and Laboratory Medicine, McGovern Medical School, Houston, TX, USA.
  • Lidov HGW; Division of Child Neurology, Department of Pediatrics, McGovern Medical School, Houston, TX, USA.
  • Harini C; Department of Neurology, McGovern Medical School, Houston, TX, USA.
  • Shah MN; Department of Radiology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
  • Leonard J; Department of Pathology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
  • Pindrik J; Department of Neurology, Boston Children's Hospital, Boston, MA, USA.
  • Shaikhouni A; Departments of Pediatric Surgery and Neurosurgery, McGovern Medical School, Houston, TX, USA.
  • Goldman JE; Department of Neurosurgery, Nationwide Children's Hospital, Columbus, OH, USA.
  • Pierson CR; Department of Neurosurgery, The Ohio State University College of Medicine, Columbus, OH, USA.
  • Thomas DL; Department of Neurosurgery, Nationwide Children's Hospital, Columbus, OH, USA.
  • Boué DR; Department of Neurosurgery, The Ohio State University College of Medicine, Columbus, OH, USA.
  • Ostendorf AP; Department of Neurosurgery, Nationwide Children's Hospital, Columbus, OH, USA.
  • Mardis ER; Department of Neurosurgery, The Ohio State University College of Medicine, Columbus, OH, USA.
  • Poduri A; Department of Pathology and Cell Biology, Columbia University, New York, NY, USA.
  • Koboldt DC; Department of Pathology and Laboratory Medicine, Nationwide Children's Hospital, Columbus, OH, USA.
  • Heinzen EL; Department of Pathology, The Ohio State University College of Medicine, Columbus, OH, USA.
  • Bedrosian TA; Department of Biomedical Education & Anatomy, Division of Anatomy, The Ohio State University College of Medicine, Columbus, OH, USA.
Nat Genet ; 55(11): 1920-1928, 2023 Nov.
Article en En | MEDLINE | ID: mdl-37872450
ABSTRACT
Somatic mosaicism is a known cause of neurological disorders, including developmental brain malformations and epilepsy. Brain mosaicism is traditionally attributed to post-zygotic genetic alterations arising in fetal development. Here we describe post-zygotic rescue of meiotic errors as an alternate origin of brain mosaicism in patients with focal epilepsy who have mosaic chromosome 1q copy number gains. Genomic analysis showed evidence of an extra parentally derived chromosome 1q allele in the resected brain tissue from five of six patients. This copy number gain is observed only in patient brain tissue, but not in blood or buccal cells, and is strongly enriched in astrocytes. Astrocytes carrying chromosome 1q gains exhibit distinct gene expression signatures and hyaline inclusions, supporting a novel genetic association for astrocytic inclusions in epilepsy. Further, these data demonstrate an alternate mechanism of brain chromosomal mosaicism, with parentally derived copy number gain isolated to brain, reflecting rescue in other tissues during development.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Epilepsias Parciales / Mosaicismo Límite: Humans Idioma: En Revista: Nat Genet Asunto de la revista: GENETICA MEDICA Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Epilepsias Parciales / Mosaicismo Límite: Humans Idioma: En Revista: Nat Genet Asunto de la revista: GENETICA MEDICA Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos