Please use this identifier to cite or link to this item: https://doi.org/10.1016/j.ajhg.2013.05.015
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dc.titleFine mapping of the 1p36 deletion syndrome identifies mutation of PRDM16 as a cause of cardiomyopathy
dc.contributor.authorArndt A.-K.
dc.contributor.authorSchafer S.
dc.contributor.authorDrenckhahn J.-D.
dc.contributor.authorSabeh M.K.
dc.contributor.authorPlovie E.R.
dc.contributor.authorCaliebe A.
dc.contributor.authorKlopocki E.
dc.contributor.authorMusso G.
dc.contributor.authorWerdich A.A.
dc.contributor.authorKalwa H.
dc.contributor.authorHeinig M.
dc.contributor.authorPadera R.F.
dc.contributor.authorWassilew K.
dc.contributor.authorBluhm J.
dc.contributor.authorHarnack C.
dc.contributor.authorMartitz J.
dc.contributor.authorBarton P.J.
dc.contributor.authorGreutmann M.
dc.contributor.authorBerger F.
dc.contributor.authorHubner N.
dc.contributor.authorSiebert R.
dc.contributor.authorKramer H.-H.
dc.contributor.authorCook S.A.
dc.contributor.authorMacrae C.A.
dc.contributor.authorKlaassen S.
dc.date.accessioned2019-01-15T08:26:31Z
dc.date.available2019-01-15T08:26:31Z
dc.date.issued2013
dc.identifier.citationArndt A.-K., Schafer S., Drenckhahn J.-D., Sabeh M.K., Plovie E.R., Caliebe A., Klopocki E., Musso G., Werdich A.A., Kalwa H., Heinig M., Padera R.F., Wassilew K., Bluhm J., Harnack C., Martitz J., Barton P.J., Greutmann M., Berger F., Hubner N., Siebert R., Kramer H.-H., Cook S.A., Macrae C.A., Klaassen S. (2013). Fine mapping of the 1p36 deletion syndrome identifies mutation of PRDM16 as a cause of cardiomyopathy. American Journal of Human Genetics 93 (1) : 67-77. ScholarBank@NUS Repository. https://doi.org/10.1016/j.ajhg.2013.05.015
dc.identifier.issn29297
dc.identifier.urihttp://scholarbank.nus.edu.sg/handle/10635/150858
dc.description.abstractDeletion 1p36 syndrome is recognized as the most common terminal deletion syndrome. Here, we describe the loss of a gene within the deletion that is responsible for the cardiomyopathy associated with monosomy 1p36, and we confirm its role in nonsyndromic left ventricular noncompaction cardiomyopathy (LVNC) and dilated cardiomyopathy (DCM). With our own data and publically available data from array comparative genomic hybridization (aCGH), we identified a minimal deletion for the cardiomyopathy associated with 1p36del syndrome that included only the terminal 14 exons of the transcription factor PRDM16 (PR domain containing 16), a gene that had previously been shown to direct brown fat determination and differentiation. Resequencing of PRDM16 in a cohort of 75 nonsyndromic individuals with LVNC detected three mutations, including one truncation mutant, one frameshift null mutation, and a single missense mutant. In addition, in a series of cardiac biopsies from 131 individuals with DCM, we found 5 individuals with 4 previously unreported nonsynonymous variants in the coding region of PRDM16. None of the PRDM16 mutations identified were observed in more than 6,400 controls. PRDM16 has not previously been associated with cardiac disease but is localized in the nuclei of cardiomyocytes throughout murine and human development and in the adult heart. Modeling of PRDM16 haploinsufficiency and a human truncation mutant in zebrafish resulted in both contractile dysfunction and partial uncoupling of cardiomyocytes and also revealed evidence of impaired cardiomyocyte proliferative capacity. In conclusion, mutation of PRDM16 causes the cardiomyopathy in 1p36 deletion syndrome as well as a proportion of nonsyndromic LVNC and DCM. ? 2013 The American Society of Human Genetics.
dc.sourceScopus
dc.typeArticle
dc.contributor.departmentDUKE-NUS MEDICAL SCHOOL
dc.description.doi10.1016/j.ajhg.2013.05.015
dc.description.sourcetitleAmerican Journal of Human Genetics
dc.description.volume93
dc.description.issue1
dc.description.page67-77
dc.description.codenAJHGA
dc.grant.idFKZ01GI0601
dc.grant.idBMBF
dc.grant.idDZHK
dc.grant.idHSCI
dc.grant.idDZHK
dc.grant.fundingagencyBMBF, Bundesministerium f�r Bildung und Forschung
dc.grant.fundingagencyBundesministerium f�r Bildung und Forschung
dc.grant.fundingagencyDeutsches Zentrum f�r Herz-Kreislaufforschung
dc.grant.fundingagencyHarvard Stem Cell Institute
dc.grant.fundingagencyDeutsches Zentrum f�r Herz-Kreislaufforschung
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