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dc.contributor.authorOchoa, Eguzkine
dc.contributor.authorLee, Sunwoo
dc.contributor.authorLan-Leung, Benoit
dc.contributor.authorDias, Renuka P
dc.contributor.authorOng, Ken K
dc.contributor.authorRadley, Jessica A
dc.contributor.authorPérez de Nanclares, Gustavo
dc.contributor.authorMartinez, Rosa
dc.contributor.authorClark, Graeme
dc.contributor.authorMartin, Ezequiel
dc.contributor.authorCastaño, Luis
dc.contributor.authorBottolo, Leonardo
dc.contributor.authorMaher, Eamonn R
dc.date.accessioned2021-12-18T00:30:35Z
dc.date.available2021-12-18T00:30:35Z
dc.date.issued2022-02
dc.identifier.issn1098-3600
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/331603
dc.description.abstractPURPOSE: Disruptions of genomic imprinting are associated with congenital imprinting disorders (CIDs) and other disease states, including cancer. CIDs are most often associated with altered methylation at imprinted differentially methylated regions (iDMRs). In some cases, multiple iDMRs are affected causing multilocus imprinting disturbances (MLIDs). The availability of accurate, quantitative, and scalable high-throughput methods to interrogate multiple iDMRs simultaneously would enhance clinical diagnostics and research. METHODS: We report the development of a custom targeted methylation sequencing panel that covered most relevant 63 iDMRs for CIDs and the detection of MLIDs. We tested it in 70 healthy controls and 147 individuals with CIDs. We distinguished loss and gain of methylation per differentially methylated region and classified high and moderate methylation alterations. RESULTS: Across a range of CIDs with a variety of molecular mechanisms, ImprintSeq performed at 98.4% sensitivity, 99.9% specificity, and 99.9% accuracy (when compared with previous diagnostic testing). ImprintSeq was highly sensitive for detecting MLIDs and enabled diagnostic criteria for MLID to be proposed. In a child with extreme MLID profile a probable genetic cause was identified. CONCLUSION: ImprintSeq provides a novel assay for clinical diagnostic and research studies of CIDs, MLIDs, and the role of disordered imprinting in human disease states.
dc.publisherElsevier BV
dc.rightsAll Rights Reserved
dc.rights.urihttp://www.rioxx.net/licenses/all-rights-reserved
dc.subjectDiagnostic assay
dc.subjectGenomic imprinting
dc.subjectImprinting disorders
dc.subjectMethylation
dc.subjectMultilocus imprinting disturbance
dc.titleImprintSeq, a novel tool to interrogate DNA methylation at human imprinted regions and diagnose multilocus imprinting disturbance.
dc.typeArticle
dc.publisher.departmentDepartment of Medical Genetics
dc.date.updated2021-12-16T15:17:06Z
prism.publicationDate2021
prism.publicationNameGenet Med
dc.identifier.doi10.17863/CAM.79055
dcterms.dateAccepted2021-10-19
rioxxterms.versionofrecord10.1016/j.gim.2021.10.011
rioxxterms.versionAM
dc.contributor.orcidOng, Kenneth [0000-0003-4689-7530]
dc.contributor.orcidBottolo, Leonardo [0000-0002-6381-2327]
dc.contributor.orcidMaher, Eamonn [0000-0002-6226-6918]
dc.identifier.eissn1530-0366
rioxxterms.typeJournal Article/Review
pubs.funder-project-idMedical Research Council (MC_UU_12015/1)
pubs.funder-project-idMedical Research Council (MC_UU_12015/2)
pubs.funder-project-idAlan Turing Institute (Unknown)
pubs.funder-project-idCambridge University Hospitals NHS Foundation Trust (CUH) (146281)
pubs.funder-project-idRosetrees Trust (A2379)
pubs.funder-project-idMRC (MC_UU_00006/2)
cam.issuedOnline2021-12-03
cam.orpheus.success2021-12-17 - Embargo set during processing via Fast-track
cam.depositDate2021-12-16
pubs.licence-identifierapollo-deposit-licence-2-1
pubs.licence-display-nameApollo Repository Deposit Licence Agreement
rioxxterms.freetoread.startdate2022-06-03


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