Patients with a Kabuki syndrome phenotype demonstrate DNA methylation abnormalities

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dc.citation.issue12
dc.citation.volume25
dc.contributor.authorSobreira, Nara
dc.contributor.authorBrucato, Martha
dc.contributor.authorZhang, Li
dc.contributor.authorLadd-Acosta, Christine
dc.contributor.authorOngaco, Chrissie
dc.contributor.authorRomm, Jane
dc.contributor.authorDoheny, Kimberly F.
dc.contributor.authorMingroni-Netto, Regina C.
dc.contributor.authorBertola, Debora
dc.contributor.authorKim, Chong A.
dc.contributor.authorPerez, Ana B. A. [UNIFESP]
dc.contributor.authorMelaragno, Maria I. [UNIFESP]
dc.contributor.authorValle, David
dc.contributor.authorMeloni, Vera A.
dc.contributor.authorBjornsson, Hans T.
dc.coverageLondon
dc.date.accessioned2020-09-01T13:21:04Z
dc.date.available2020-09-01T13:21:04Z
dc.date.issued2017
dc.description.abstractKabuki syndrome is a monogenic disorder caused by loss of function variants in either of two genes encoding histone-modifying enzymes. We performed targeted sequencing in a cohort of 27 probands with a clinical diagnosis of Kabuki syndrome. Of these, 12 had causative variants in the two known Kabuki syndrome genes. In 2, we identified presumptive loss of function de novo variants in KMT2A (missense and splice site variants), a gene that encodes another histone modifying enzyme previously exclusively associated with Wiedermann-Steiner syndrome. Although Kabuki syndrome is a disorder of histone modification, we also find alterations in DNA methylation among individuals with a Kabuki syndrome diagnosis relative to matched normal controls, regardless of whether they carry a variant in KMT2A or KMT2D or not. Furthermore, we observed characteristic global abnormalities of DNA methylation that distinguished patients with a loss of function variant in KMT2D or missense or splice site variants in either KMT2D or KMT2A from normal controls. Our results provide new insights into the relationship of genotype to epigenotype and phenotype and indicate cross-talk between histone and DNA methylation machineries exposed by inborn errors of the epigenetic apparatus.en
dc.description.affiliationJohns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD 21218 USA
dc.description.affiliationJohns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21205 USA
dc.description.affiliationJohns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA
dc.description.affiliationJohns Hopkins Univ, Sch Med, Inst Med Genet, CIDR, Baltimore, MD USA
dc.description.affiliationUniv Sao Paulo, Inst Biociencias, Dept Genet & Biol Evolut, Rua Matao 277, BR-05508090 Sao Paulo, Brazil
dc.description.affiliationUniv Sao Paulo, Fac Med, Hosp Clin, Unidade Genet,Inst Crianca, Sao Paulo, Brazil
dc.description.affiliationUniv Fed Sao Paulo, Dept Morphol & Genet, Genet Div, Sao Paulo, Brazil
dc.description.affiliationUniv Iceland, Fac Med, Reykjavik, Iceland
dc.description.affiliationUnifespUniv Fed Sao Paulo, Dept Morphol & Genet, Genet Div, Sao Paulo, Brazil
dc.description.provenanceMade available in DSpace on 2020-09-01T13:21:04Z (GMT). No. of bitstreams: 0 Previous issue date: 2017en
dc.description.sourceWeb of Science
dc.description.sponsorshipNIH Director's Early Independence Award [DP5OD017877]
dc.description.sponsorshipNational Human Genome Research Institute [1U54HG006493]
dc.format.extent1335-1344
dc.identifierhttp://dx.doi.org/10.1038/s41431-017-0023-0
dc.identifier.citationEuropean Journal Of Human Genetics. London, v. 25, n. 12, p. 1335-1344, 2017.
dc.identifier.doi10.1038/s41431-017-0023-0
dc.identifier.issn1018-4813
dc.identifier.urihttps://repositorio.unifesp.br/handle/11600/58073
dc.identifier.wosWOS:000418403600005
dc.language.isoeng
dc.publisherNature Publishing Group
dc.relation.ispartofEuropean Journal Of Human Genetics
dc.rightsAcesso restrito
dc.titlePatients with a Kabuki syndrome phenotype demonstrate DNA methylation abnormalitiesen
dc.typeArtigo
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