Welcome to the UPF Digital Repository

Comprehensive multi-omic profiling of somatic mutations in malformations of cortical development

Show simple item record

dc.contributor.author Chung, Changuk
dc.contributor.author Brain Somatic Mosaicism Network
dc.contributor.author Gleeson, Joseph G.
dc.date.accessioned 2023-09-28T06:20:45Z
dc.date.available 2023-09-28T06:20:45Z
dc.date.issued 2023
dc.identifier.citation Chung C, Yang X, Bae T, Vong KI, Mittal S, Donkels C, et al. Comprehensive multi-omic profiling of somatic mutations in malformations of cortical development. Nat Genet. 2023 Feb;55(2):209-20. DOI: 10.1038/s41588-022-01276-9
dc.identifier.issn 1061-4036
dc.identifier.uri http://hdl.handle.net/10230/57986
dc.description.abstract Malformations of cortical development (MCD) are neurological conditions involving focal disruptions of cortical architecture and cellular organization that arise during embryogenesis, largely from somatic mosaic mutations, and cause intractable epilepsy. Identifying the genetic causes of MCD has been a challenge, as mutations remain at low allelic fractions in brain tissue resected to treat condition-related epilepsy. Here we report a genetic landscape from 283 brain resections, identifying 69 mutated genes through intensive profiling of somatic mutations, combining whole-exome and targeted-amplicon sequencing with functional validation including in utero electroporation of mice and single-nucleus RNA sequencing. Genotype-phenotype correlation analysis elucidated specific MCD gene sets associated with distinct pathophysiological and clinical phenotypes. The unique single-cell level spatiotemporal expression patterns of mutated genes in control and patient brains indicate critical roles in excitatory neurogenic pools during brain development and in promoting neuronal hyperexcitability after birth.
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher Nature Research
dc.relation.ispartof Nat Genet. 2023 Feb;55(2):209-20
dc.rights © Springer Nature Publishing AG [Chung C, Yang X, Bae T, Vong KI, Mittal S, Donkels C, et al. Comprehensive multi-omic profiling of somatic mutations in malformations of cortical development. Nat Genet. 2023 Feb;55(2):209-20. DOI: 10.1038/s41588-022-01276-9] [http://dx.doi.org/10.1038/s41588-022-01276-9]
dc.title Comprehensive multi-omic profiling of somatic mutations in malformations of cortical development
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.1038/s41588-022-01276-9
dc.subject.keyword Genetics research
dc.subject.keyword Neurogenesis
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/acceptedVersion

Thumbnail

This item appears in the following Collection(s)

Show simple item record

Search DSpace


Advanced Search

Browse

My Account

Statistics

In collaboration with Compliant to Partaking