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dc.contributor.authorBilgüvar, Kaya
dc.contributor.authorÖztürk, Ali Kemal
dc.contributor.authorLouvi, Angeliki
dc.contributor.authorKwan, Kenneth Y
dc.contributor.authorChoi, Murim
dc.contributor.authorTatli, Burak
dc.contributor.authorYalnizoğlu, Dilek
dc.contributor.authorTüysüz, Beyhan
dc.contributor.authorÇağlayan, Ahmet Okay
dc.contributor.authorGökben, Sarenur
dc.contributor.authorKaymakçalan, Hande
dc.contributor.authorBarak, Tanyeri
dc.contributor.authorBakircioğlu, Mehmet
dc.contributor.authorYasuno, Katsuhito
dc.contributor.authorHo, Winson
dc.contributor.authorSanders, Stephan
dc.contributor.authorZhu, Ying
dc.contributor.authorYilmaz, Sanem
dc.contributor.authorDinçer, Alp
dc.contributor.authorJohnson, Michele H
dc.contributor.authorBronen, Richard A
dc.contributor.authorKoçer, Naci
dc.contributor.authorPer, Hüseyin
dc.contributor.authorMane, Shrikant
dc.contributor.authorPamir, Mehmet Necmettin
dc.contributor.authorYalçinkaya, Cengiz
dc.contributor.authorKumandaş, Sefer
dc.contributor.authorTopçu, Meral
dc.contributor.authorÖzmen, Meral
dc.contributor.authorŠestan, Nenad
dc.contributor.authorLifton, Richard P
dc.contributor.authorState, Matthew W
dc.contributor.authorGünel, Murat
dc.date.accessioned2019-12-10T10:52:12Z
dc.date.available2019-12-10T10:52:12Z
dc.date.issued2010
dc.identifier.issn0028-0836
dc.identifier.urihttps://doi.org/10.1038/nature09327
dc.identifier.urihttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3129007/
dc.identifier.urihttp://hdl.handle.net/11655/14519
dc.description.abstractThe development of the human cerebral cortex is an orchestrated process involving the birth of neural progenitors in the peri-ventricular germinal zones, cell proliferation characterized by both symmetric and asymmetric mitoses, followed by migration of post-mitotic neurons to their final destinations in 6 highly ordered, functionally-specialized layers,. An understanding of the molecular mechanisms guiding these intricate processes is in its infancy, substantially driven by the discovery of rare mutations that cause malformations of cortical development (MCD)-. Mapping of disease loci in putative Mendelian forms of MCD has been hindered by marked locus heterogeneity, small kindred sizes and diagnostic classifications that may not reflect molecular pathogenesis. Here we demonstrate the use of whole-exome sequencing to overcome these obstacles by identifying recessive mutations in WDR62 as the cause of a wide spectrum of severe cerebral cortical malformations including microcephaly, pachygria with cortical thickening as well as hypoplasia of the corpus callosum. Some patients with WDR62 mutations had evidence of additional abnormalities including lissencephaly, schizencephaly, polymicrogyria and, in one instance, cerebellar hypoplasia, all traits traditionally regarded as distinct entities. In mouse and humans, WDR62 transcripts and protein are enriched in neural progenitors within the ventricular and subventricular zones. WDR62 expression in the neocortex is transient, spanning the period of embryonic neurogenesis. Unlike other known microcephaly genes, WDR62 does not apparently associate with centrosomes and is predominantly nuclear in localization. These findings unify previously disparate aspects of cerebral cortical development and highlight the utility of whole-exome sequencing to identify disease loci in settings in which traditional methods have proved challenging.
dc.language.isoen
dc.relation.isversionof10.1038/nature09327
dc.rightsinfo:eu-repo/semantics/openAccess
dc.titleWhole Exome Sequencing Identifies Recessive Wdr62 Mutations In Severe Brain Malformations
dc.typeinfo:eu-repo/semantics/article
dc.typeinfo:eu-repo/semantics/publishedVersion
dc.typeinfo:eu-repo/semantics/publishedVersion
dc.relation.journalNature
dc.contributor.departmentÇocuk Sağlığı ve Hastalıkları
dc.identifier.volume467
dc.identifier.issue7312
dc.identifier.startpage207
dc.identifier.endpage210
dc.description.indexPubMed
dc.description.indexWoS


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