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dc.contributor.authorQuintero-Rivera, Fabiolaen_US
dc.contributor.authorXi, Qiongchao J.en_US
dc.contributor.authorKeppler-Noreuil, Kim M.en_US
dc.contributor.authorLee, Ji Hyunen_US
dc.contributor.authorHiggins, Anne W.en_US
dc.contributor.authorAnchan, Raymond M.en_US
dc.contributor.authorRoberts, Amy E.en_US
dc.contributor.authorSeong, Ihn Siken_US
dc.contributor.authorFan, Xuepingen_US
dc.contributor.authorLage, Kasperen_US
dc.contributor.authorLu, Lily Y.en_US
dc.contributor.authorTao, Joannaen_US
dc.contributor.authorHu, Xuchenen_US
dc.contributor.authorBerezney, Ronalden_US
dc.contributor.authorGelb, Bruce D.en_US
dc.contributor.authorKamp, Annaen_US
dc.contributor.authorMoskowitz, Ivan P.en_US
dc.contributor.authorLacro, Ronald V.en_US
dc.contributor.authorLu, Weiningen_US
dc.contributor.authorMorton, Cynthia C.en_US
dc.contributor.authorGusella, James F.en_US
dc.contributor.authorMaas, Richard L.en_US
dc.date.accessioned2015-05-04T15:27:56Z
dc.date.issued2015en_US
dc.identifier.citationQuintero-Rivera, F., Q. J. Xi, K. M. Keppler-Noreuil, J. H. Lee, A. W. Higgins, R. M. Anchan, A. E. Roberts, et al. 2015. “MATR3 disruption in human and mouse associated with bicuspid aortic valve, aortic coarctation and patent ductus arteriosus.” Human Molecular Genetics 24 (8): 2375-2389. doi:10.1093/hmg/ddv004. http://dx.doi.org/10.1093/hmg/ddv004.en
dc.identifier.issn0964-6906en
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:15035026
dc.description.abstractCardiac left ventricular outflow tract (LVOT) defects represent a common but heterogeneous subset of congenital heart disease for which gene identification has been difficult. We describe a 46,XY,t(1;5)(p36.11;q31.2)dn translocation carrier with pervasive developmental delay who also exhibited LVOT defects, including bicuspid aortic valve (BAV), coarctation of the aorta (CoA) and patent ductus arteriosus (PDA). The 1p breakpoint disrupts the 5′ UTR of AHDC1, which encodes AT-hook DNA-binding motif containing-1 protein, and AHDC1-truncating mutations have recently been described in a syndrome that includes developmental delay, but not congenital heart disease [Xia, F., Bainbridge, M.N., Tan, T.Y., Wangler, M.F., Scheuerle, A.E., Zackai, E.H., Harr, M.H., Sutton, V.R., Nalam, R.L., Zhu, W. et al. (2014) De Novo truncating mutations in AHDC1 in individuals with syndromic expressive language delay, hypotonia, and sleep apnea. Am. J. Hum. Genet., 94, 784–789]. On the other hand, the 5q translocation breakpoint disrupts the 3′ UTR of MATR3, which encodes the nuclear matrix protein Matrin 3, and mouse Matr3 is strongly expressed in neural crest, developing heart and great vessels, whereas Ahdc1 is not. To further establish MATR3 3′ UTR disruption as the cause of the proband's LVOT defects, we prepared a mouse Matr3Gt-ex13 gene trap allele that disrupted the 3′ portion of the gene. Matr3Gt-ex13 homozygotes are early embryo lethal, but Matr3Gt-ex13 heterozygotes exhibit incompletely penetrant BAV, CoA and PDA phenotypes similar to those in the human proband, as well as ventricular septal defect (VSD) and double-outlet right ventricle (DORV). Both the human MATR3 translocation breakpoint and the mouse Matr3Gt-ex13 gene trap insertion disturb the polyadenylation of MATR3 transcripts and alter Matrin 3 protein expression, quantitatively or qualitatively. Thus, subtle perturbations in Matrin 3 expression appear to cause similar LVOT defects in human and mouse.en
dc.language.isoen_USen
dc.publisherOxford University Pressen
dc.relation.isversionofdoi:10.1093/hmg/ddv004en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC4380077/pdf/en
dash.licenseLAAen_US
dc.titleMATR3 disruption in human and mouse associated with bicuspid aortic valve, aortic coarctation and patent ductus arteriosusen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalHuman Molecular Geneticsen
dash.depositing.authorAnchan, Raymond M.en_US
dc.date.available2015-05-04T15:27:56Z
dc.identifier.doi10.1093/hmg/ddv004*
dash.authorsorderedfalse
dash.contributor.affiliatedSeong, Ihn
dash.contributor.affiliatedMorton, Cynthia
dash.contributor.affiliatedAnchan, Raymond
dash.contributor.affiliatedRoberts, Amy
dash.contributor.affiliatedGusella, James


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