Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/12352
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dc.contributor.authorJamuar, Saumya Sen
dc.contributor.authorLam, Anh-Thu Nen
dc.contributor.authorKircher, Martinen
dc.contributor.authorD'Gama, Alissa Men
dc.contributor.authorWang, Jianen
dc.contributor.authorBarry, Brenda Jen
dc.contributor.authorZhang, Xiaochangen
dc.contributor.authorHill, Robert Seanen
dc.contributor.authorPartlow, Jennifer Nen
dc.contributor.authorRozzo, Aldoen
dc.contributor.authorServattalab, Sarahen
dc.contributor.authorMehta, Bhaven Ken
dc.contributor.authorTopcu, Meralen
dc.contributor.authorAmrom, Dinaen
dc.contributor.authorAndermann, Evaen
dc.contributor.authorDan, Bernarden
dc.contributor.authorParrini, Elenaen
dc.contributor.authorGuerrini, Renzoen
dc.contributor.authorScheffer, Ingrid Een
dc.contributor.authorBerkovic, Samuel Fen
dc.contributor.authorLeventer, Richard Jen
dc.contributor.authorShen, Yipingen
dc.contributor.authorWu, Bai Linen
dc.contributor.authorBarkovich, A Jamesen
dc.contributor.authorSahin, Mustafaen
dc.contributor.authorChang, Bernard Sen
dc.contributor.authorBamshad, Michaelen
dc.contributor.authorNickerson, Deborah Aen
dc.contributor.authorShendure, Jayen
dc.contributor.authorPoduri, Annapurnaen
dc.contributor.authorYu, Timothy Wen
dc.contributor.authorWalsh, Christopher Aen
dc.date.accessioned2015-05-16T02:02:28Z
dc.date.available2015-05-16T02:02:28Z
dc.date.issued2014-08-21en
dc.identifier.citationThe New England Journal of Medicine; 371(8): 733-43en
dc.identifier.govdoc25140959en
dc.identifier.otherPUBMEDen
dc.identifier.urihttps://ahro.austin.org.au/austinjspui/handle/1/12352en
dc.description.abstractAlthough there is increasing recognition of the role of somatic mutations in genetic disorders, the prevalence of somatic mutations in neurodevelopmental disease and the optimal techniques to detect somatic mosaicism have not been systematically evaluated.Using a customized panel of known and candidate genes associated with brain malformations, we applied targeted high-coverage sequencing (depth, ≥200×) to leukocyte-derived DNA samples from 158 persons with brain malformations, including the double-cortex syndrome (subcortical band heterotopia, 30 persons), polymicrogyria with megalencephaly (20), periventricular nodular heterotopia (61), and pachygyria (47). We validated candidate mutations with the use of Sanger sequencing and, for variants present at unequal read depths, subcloning followed by colony sequencing.Validated, causal mutations were found in 27 persons (17%; range, 10 to 30% for each phenotype). Mutations were somatic in 8 of the 27 (30%), predominantly in persons with the double-cortex syndrome (in whom we found mutations in DCX and LIS1), persons with periventricular nodular heterotopia (FLNA), and persons with pachygyria (TUBB2B). Of the somatic mutations we detected, 5 (63%) were undetectable with the use of traditional Sanger sequencing but were validated through subcloning and subsequent sequencing of the subcloned DNA. We found potentially causal mutations in the candidate genes DYNC1H1, KIF5C, and other kinesin genes in persons with pachygyria.Targeted sequencing was found to be useful for detecting somatic mutations in patients with brain malformations. High-coverage sequencing panels provide an important complement to whole-exome and whole-genome sequencing in the evaluation of somatic mutations in neuropsychiatric disease. (Funded by the National Institute of Neurological Disorders and Stroke and others.).en
dc.language.isoenen
dc.subject.otherCerebral Cortex.abnormalitiesen
dc.subject.otherClassical Lissencephalies and Subcortical Band Heterotopias.geneticsen
dc.subject.otherDNA Mutational Analysis.methodsen
dc.subject.otherHumansen
dc.subject.otherLissencephaly.geneticsen
dc.subject.otherMagnetic Resonance Imagingen
dc.subject.otherMalformations of Cortical Development.genetics.pathologyen
dc.subject.otherMutationen
dc.subject.otherPeriventricular Nodular Heterotopia.geneticsen
dc.titleSomatic mutations in cerebral cortical malformations.en
dc.typeJournal Articleen
dc.identifier.journaltitleThe New England Journal of Medicineen
dc.identifier.affiliationFrom the Division of Genetics and Genomics, Manton Center for Orphan Disease Research, Howard Hughes Medical Institute (S.S.J., A.-T.N.L., A.M.D., B.J.B., X.Z., R.S.H., J.N.P., A.R., S.S., B.K.M., T.W.Y., C.A.W.), and the Departments of Laboratory Medicine (J.W., Y.S., B.L.W.) and Neurology (M.S., A.P.), Boston Children's Hospital, the Departments of Pediatrics (S.S.J., A.-T.N.L., A.M.D., B.J.B., X.Z., R.S.H., J.N.P., A.R., S.S., B.K.M., T.W.Y., C.A.W.), Neurology (S.S.J., A.-T.N.L., A.M.D., B.J.B., X.Z., R.S.H., J.N.P., A.R., S.S., B.K.M., T.W.Y., C.A.W., M.S., A.P.), and Pathology (Y.S., B.L.W.), Harvard Medical School, the Department of Neurology, Beth Israel Deaconess Medical Center (B.S.C.), and the Department of Neurology, Massachusetts General Hospital (T.W.Y.) - all in Boston; the Department of Paediatrics, KK Women's and Children's Hospital, Singapore, Singapore (S.S.J.); the Department of Genome Sciences, University of Washington, Seattle (M.K., M.B., D.A.N., J.S.); the Department of Laboratory Medicine, Shanghai Children's Medical Center, Shanghai (J.W., Y.S.); the Division of Neurology, Department of Pediatrics, Hacettepe University School of Medicine, Sihhiye, Ankara, Turkey (M.T.); the Neurogenetics Unit, Montreal Neurological Hospital and Institute, Department of Neurology and Neurosurgery (D.A., E.A.) and Department of Human Genetics (E.A.), McGill University, Montreal; the Department of Neurology, Hôpital Universitaire des Enfants Reine Fabiola, Université Libre de Bruxelles, Brussels (B.D.); the Pediatric Neurology Unit and Laboratories, Children's Hospital A. Meyer-University of Florence, Florence, Italy (E.P., R.G.); the Department of Medicine, University of Melbourne, Austin Health, Heidelberg (I.E.S., S.F.B.), Department of Paediatrics, Royal Children's Hospital, University of Melbourne, and the Florey Institute of Neuroscience and Mental Health, Melbourne (I.E.S.), and the Department of Neurology, Royal Children's Hospital, Murdoch Children'en
dc.identifier.doi10.1056/NEJMoa1314432en
dc.description.pages733-43en
dc.relation.urlhttps://pubmed.ncbi.nlm.nih.gov/25140959en
dc.type.austinJournal Articleen
local.name.researcherBerkovic, Samuel F
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.cerifentitytypePublications-
item.fulltextNo Fulltext-
item.grantfulltextnone-
item.languageiso639-1en-
item.openairetypeJournal Article-
crisitem.author.deptEpilepsy Research Centre-
crisitem.author.deptEpilepsy Research Centre-
crisitem.author.deptNeurology-
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