دورية أكاديمية
Post-zygotic rescue of meiotic errors causes brain mosaicism and focal epilepsy.
| العنوان: | Post-zygotic rescue of meiotic errors causes brain mosaicism and focal epilepsy. |
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| المؤلفون: | Miller KE; Institute for Genomic Medicine, Nationwide Children's Hospital, Columbus, OH, USA.; Department of Pediatrics, The Ohio State University, Columbus, OH, USA., Rivaldi AC; Institute for Genomic Medicine, Nationwide Children's Hospital, 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; Department of Pediatrics, The Ohio State University, Columbus, OH, USA., Akkari Y; Institute for Genomic Medicine, Nationwide Children's Hospital, 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.; Department of Pediatrics, The Ohio State University, Columbus, OH, USA., Marhabaie M; Institute for Genomic Medicine, Nationwide Children's Hospital, Columbus, OH, USA., Gade M; Division of Pharmacotherapy and Experimental Therapeutics in the Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Lu J; Division of Pharmacotherapy and Experimental Therapeutics in the Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Rodziyevska O; Division of Child Neurology, Department of Pediatrics, McGovern Medical School, Houston, TX, USA., Bhattacharjee MB; Department of Pathology and Laboratory Medicine, McGovern Medical School, Houston, TX, USA., Von Allmen GK; Division of Child Neurology, Department of Pediatrics, McGovern Medical School, Houston, TX, USA.; Department of Neurology, McGovern Medical School, Houston, TX, USA., Yang E; Department of Radiology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA., Lidov HGW; Department of Pathology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA., Harini C; Department of Neurology, Boston Children's Hospital, Boston, MA, USA., Shah MN; Departments of Pediatric Surgery and Neurosurgery, McGovern Medical School, Houston, TX, USA., Leonard J; Department of Neurosurgery, Nationwide Children's Hospital, Columbus, OH, USA.; Department of Neurosurgery, The Ohio State University College of Medicine, Columbus, OH, USA., Pindrik J; Department of Neurosurgery, Nationwide Children's Hospital, Columbus, OH, USA.; Department of Neurosurgery, The Ohio State University College of Medicine, Columbus, OH, USA., Shaikhouni A; Department of Neurosurgery, Nationwide Children's Hospital, Columbus, OH, USA.; Department of Neurosurgery, The Ohio State University College of Medicine, Columbus, OH, USA., Goldman JE; Department of Pathology and Cell Biology, Columbia University, New York, NY, USA., Pierson CR; Department of Pathology and Laboratory Medicine, Nationwide Children's Hospital, Columbus, OH, USA.; Department of Pathology, The Ohio State University College of Medicine, Columbus, OH, USA.; Department of Biomedical Education & Anatomy, Division of Anatomy, The Ohio State University College of Medicine, Columbus, OH, USA., Thomas DL; Department of Pathology and Laboratory Medicine, Nationwide Children's Hospital, Columbus, OH, USA.; Department of Pathology, The Ohio State University College of Medicine, Columbus, OH, USA., Boué DR; Department of Pathology and Laboratory Medicine, Nationwide Children's Hospital, Columbus, OH, USA.; Department of Pathology, The Ohio State University College of Medicine, Columbus, OH, USA., Ostendorf AP; Department of Pediatrics, The Ohio State University, Columbus, OH, USA.; Division of Pediatric Neurology, Nationwide Children's Hospital, Columbus, OH, USA., Mardis ER; Institute for Genomic Medicine, Nationwide Children's Hospital, Columbus, OH, USA.; Department of Neurosurgery, The Ohio State University College of Medicine, Columbus, OH, USA., Poduri A; Department of Neurology, Boston Children's Hospital, Boston, MA, USA., Koboldt DC; Institute for Genomic Medicine, Nationwide Children's Hospital, Columbus, OH, USA.; Department of Pediatrics, The Ohio State University, Columbus, OH, USA., Heinzen EL; Division of Pharmacotherapy and Experimental Therapeutics in the Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. erin-h@email.unc.edu.; Department of Genetics in the School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. erin-h@email.unc.edu., Bedrosian TA; Institute for Genomic Medicine, Nationwide Children's Hospital, Columbus, OH, USA. tracy.bedrosian@nationwidechildrens.org.; Department of Pediatrics, The Ohio State University, Columbus, OH, USA. tracy.bedrosian@nationwidechildrens.org. |
| المصدر: | Nature genetics [Nat Genet] 2023 Nov; Vol. 55 (11), pp. 1920-1928. Date of Electronic Publication: 2023 Oct 23. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Nature Pub. Co Country of Publication: United States NLM ID: 9216904 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1546-1718 (Electronic) Linking ISSN: 10614036 NLM ISO Abbreviation: Nat Genet Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: New York, NY : Nature Pub. Co., c1992- |
| مواضيع طبية MeSH: | Mosaicism* , Epilepsies, Partial*/genetics, Humans ; Mouth Mucosa ; Mutation ; Brain |
| مستخلص: | 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. (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.) |
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Innovation 2, 100141 (2021). (PMID: 345577788454663) |
| معلومات مُعتمدة: | P50 HD105351 United States HD NICHD NIH HHS; R01 NS094596 United States NS NINDS NIH HHS; R01 NS129784 United States NS NINDS NIH HHS; T32 GM139784 United States GM NIGMS NIH HHS |
| تواريخ الأحداث: | Date Created: 20231023 Date Completed: 20231110 Latest Revision: 20240502 |
| رمز التحديث: | 20240502 |
| مُعرف محوري في PubMed: | PMC10714261 |
| DOI: | 10.1038/s41588-023-01547-z |
| PMID: | 37872450 |
| قاعدة البيانات: | MEDLINE |
Find this article in full text from Springer Verlag. 
Full Text Finder | تدمد: | 1546-1718 |
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| DOI: | 10.1038/s41588-023-01547-z |