{"@context":{"@vocab":"https://cir.nii.ac.jp/schema/1.0/","rdfs":"http://www.w3.org/2000/01/rdf-schema#","dc":"http://purl.org/dc/elements/1.1/","dcterms":"http://purl.org/dc/terms/","foaf":"http://xmlns.com/foaf/0.1/","prism":"http://prismstandard.org/namespaces/basic/2.0/","cinii":"http://ci.nii.ac.jp/ns/1.0/","datacite":"https://schema.datacite.org/meta/kernel-4/","ndl":"http://ndl.go.jp/dcndl/terms/","jpcoar":"https://github.com/JPCOAR/schema/blob/master/2.0/"},"@id":"https://cir.nii.ac.jp/crid/1363388846196935552.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.1161/circgenetics.113.000011"}},{"identifier":{"@type":"URI","@value":"https://www.ahajournals.org/doi/full/10.1161/CIRCGENETICS.113.000011"}}],"dc:title":[{"@value":"Whole Exome Sequencing Identifies a Causal\n            <i>RBM20</i>\n            Mutation in a Large Pedigree With Familial Dilated Cardiomyopathy"}],"description":[{"type":"abstract","notation":[{"@value":"<jats:sec>\n            <jats:title>Background—</jats:title>\n            <jats:p>Whole exome sequencing is a powerful technique for Mendelian disease gene discovery. However, variant prioritization remains a challenge. We applied whole exome sequencing to identify the causal variant in a large family with familial dilated cardiomyopathy of unknown pathogenesis.</jats:p>\n          </jats:sec>\n          <jats:sec>\n            <jats:title>Methods and Results—</jats:title>\n            <jats:p>\n              A large family with autosomal dominant, familial dilated cardiomyopathy was identified. Exome capture and sequencing were performed in 3 remotely related, affected subjects predicted to share <0.1% of their genomes by descent. Shared variants were filtered for rarity, evolutionary conservation, and predicted functional significance, and remaining variants were filtered against 71 locally generated exomes. Variants were also prioritized using the Variant Annotation Analysis and Search Tool. Final candidates were validated by Sanger sequencing and tested for segregation. There were 664 shared heterozygous nonsense, missense, or splice site variants, of which 26 were rare (minor allele frequency ≤0.001 or not reported) in 2 public databases. Filtering against internal exomes reduced the number of candidates to 2, and of these, a single variant (c.1907 G>A) in\n              <jats:italic>RBM20</jats:italic>\n              , segregated with disease status and was absent in unaffected internal reference exomes. Bioinformatic prioritization with Variant Annotation Analysis and Search Tool supported this result.\n            </jats:p>\n          </jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions—</jats:title>\n            <jats:p>\n              Whole exome sequencing of remotely related dilated cardiomyopathy subjects from a large, multiplex family, followed by systematic filtering, identified a causal\n              <jats:italic>RBM20</jats:italic>\n              mutation without the need for linkage analysis.\n            </jats:p>\n          </jats:sec>"}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1383388846196935561","@type":"Researcher","foaf:name":[{"@value":"Quinn S. Wells"}],"jpcoar:affiliationName":[{"@value":"From the Divisions of Cardiovascular Medicine (Q.S.W., J.R.B., Y.R.S., N.L.A., A.J.N., L.M., D.M.R., C.C.H.), Clinical Pharmacology (J.D.M., P.W., N.L.A., A.H.R., D.M.R.), Center for Inherited Heart Disease (Q.S.W., J.R.B., N.L.A., J.P.P., L.M., V.E., D.M.R., C.C.H.), Center for Human Genetics Research (L.D’.A.), Division of Medical Genetics and Genomic Medicine (J.P.P.), Department of Pediatric Cardiology (L.M., V.E.), and Departments of Pharmacology and Cell and Developmental Biology (C.C.H.),..."}]},{"@id":"https://cir.nii.ac.jp/crid/1383388846196935557","@type":"Researcher","foaf:name":[{"@value":"Jason R. Becker"}],"jpcoar:affiliationName":[{"@value":"From the Divisions of Cardiovascular Medicine (Q.S.W., J.R.B., Y.R.S., N.L.A., A.J.N., L.M., D.M.R., C.C.H.), Clinical Pharmacology (J.D.M., P.W., N.L.A., A.H.R., D.M.R.), Center for Inherited Heart Disease (Q.S.W., J.R.B., N.L.A., J.P.P., L.M., V.E., D.M.R., C.C.H.), Center for Human Genetics Research (L.D’.A.), Division of Medical Genetics and Genomic Medicine (J.P.P.), Department of Pediatric Cardiology (L.M., V.E.), and Departments of Pharmacology and Cell and Developmental Biology (C.C.H.),..."}]},{"@id":"https://cir.nii.ac.jp/crid/1383388846196935563","@type":"Researcher","foaf:name":[{"@value":"Yan R. Su"}],"jpcoar:affiliationName":[{"@value":"From the Divisions of Cardiovascular Medicine (Q.S.W., J.R.B., Y.R.S., N.L.A., A.J.N., L.M., D.M.R., C.C.H.), Clinical Pharmacology (J.D.M., P.W., N.L.A., A.H.R., D.M.R.), Center for Inherited Heart Disease (Q.S.W., J.R.B., N.L.A., J.P.P., L.M., V.E., D.M.R., C.C.H.), Center for Human Genetics Research (L.D’.A.), Division of Medical Genetics and Genomic Medicine (J.P.P.), Department of Pediatric Cardiology (L.M., V.E.), and Departments of Pharmacology and Cell and Developmental Biology (C.C.H.),..."}]},{"@id":"https://cir.nii.ac.jp/crid/1383388846196935555","@type":"Researcher","foaf:name":[{"@value":"Jonathan D. Mosley"}],"jpcoar:affiliationName":[{"@value":"From the Divisions of Cardiovascular Medicine (Q.S.W., J.R.B., Y.R.S., N.L.A., A.J.N., L.M., D.M.R., C.C.H.), Clinical Pharmacology (J.D.M., P.W., N.L.A., A.H.R., D.M.R.), Center for Inherited Heart Disease (Q.S.W., J.R.B., N.L.A., J.P.P., L.M., V.E., D.M.R., C.C.H.), Center for Human Genetics Research (L.D’.A.), Division of Medical Genetics and Genomic Medicine (J.P.P.), Department of Pediatric Cardiology (L.M., V.E.), and Departments of Pharmacology and Cell and Developmental Biology (C.C.H.),..."}]},{"@id":"https://cir.nii.ac.jp/crid/1383388846196935556","@type":"Researcher","foaf:name":[{"@value":"Peter Weeke"}],"jpcoar:affiliationName":[{"@value":"From the Divisions of Cardiovascular Medicine (Q.S.W., J.R.B., Y.R.S., N.L.A., A.J.N., L.M., D.M.R., C.C.H.), Clinical Pharmacology (J.D.M., P.W., N.L.A., A.H.R., D.M.R.), Center for Inherited Heart Disease (Q.S.W., J.R.B., N.L.A., J.P.P., L.M., V.E., D.M.R., C.C.H.), Center for Human Genetics Research (L.D’.A.), Division of Medical Genetics and Genomic Medicine (J.P.P.), Department of Pediatric Cardiology (L.M., V.E.), and Departments of Pharmacology and Cell and Developmental Biology (C.C.H.),..."}]},{"@id":"https://cir.nii.ac.jp/crid/1383388846196935562","@type":"Researcher","foaf:name":[{"@value":"Laura D’Aoust"}],"jpcoar:affiliationName":[{"@value":"From the Divisions of Cardiovascular Medicine (Q.S.W., J.R.B., Y.R.S., N.L.A., A.J.N., L.M., D.M.R., C.C.H.), Clinical Pharmacology (J.D.M., P.W., N.L.A., A.H.R., D.M.R.), Center for Inherited Heart Disease (Q.S.W., J.R.B., N.L.A., J.P.P., L.M., V.E., D.M.R., C.C.H.), Center for Human Genetics Research (L.D’.A.), Division of Medical Genetics and Genomic Medicine (J.P.P.), Department of Pediatric Cardiology (L.M., V.E.), and Departments of Pharmacology and Cell and Developmental Biology (C.C.H.),..."}]},{"@id":"https://cir.nii.ac.jp/crid/1383388846196935560","@type":"Researcher","foaf:name":[{"@value":"Natalie L. Ausborn"}],"jpcoar:affiliationName":[{"@value":"From the Divisions of Cardiovascular Medicine (Q.S.W., J.R.B., Y.R.S., N.L.A., A.J.N., L.M., D.M.R., C.C.H.), Clinical Pharmacology (J.D.M., P.W., N.L.A., A.H.R., D.M.R.), Center for Inherited Heart Disease (Q.S.W., J.R.B., N.L.A., J.P.P., L.M., V.E., D.M.R., C.C.H.), Center for Human Genetics Research (L.D’.A.), Division of Medical Genetics and Genomic Medicine (J.P.P.), Department of Pediatric Cardiology (L.M., V.E.), and Departments of Pharmacology and Cell and Developmental Biology (C.C.H.),..."}]},{"@id":"https://cir.nii.ac.jp/crid/1383388846196935425","@type":"Researcher","foaf:name":[{"@value":"Andrea H. Ramirez"}],"jpcoar:affiliationName":[{"@value":"From the Divisions of Cardiovascular Medicine (Q.S.W., J.R.B., Y.R.S., N.L.A., A.J.N., L.M., D.M.R., C.C.H.), Clinical Pharmacology (J.D.M., P.W., N.L.A., A.H.R., D.M.R.), Center for Inherited Heart Disease (Q.S.W., J.R.B., N.L.A., J.P.P., L.M., V.E., D.M.R., C.C.H.), Center for Human Genetics Research (L.D’.A.), Division of Medical Genetics and Genomic Medicine (J.P.P.), Department of Pediatric Cardiology (L.M., V.E.), and Departments of Pharmacology and Cell and Developmental Biology (C.C.H.),..."}]},{"@id":"https://cir.nii.ac.jp/crid/1383388846196935559","@type":"Researcher","foaf:name":[{"@value":"Jean P. Pfotenhauer"}],"jpcoar:affiliationName":[{"@value":"From the Divisions of Cardiovascular Medicine (Q.S.W., J.R.B., Y.R.S., N.L.A., A.J.N., L.M., D.M.R., C.C.H.), Clinical Pharmacology (J.D.M., P.W., N.L.A., A.H.R., D.M.R.), Center for Inherited Heart Disease (Q.S.W., J.R.B., N.L.A., J.P.P., L.M., V.E., D.M.R., C.C.H.), Center for Human Genetics Research (L.D’.A.), Division of Medical Genetics and Genomic Medicine (J.P.P.), Department of Pediatric Cardiology (L.M., V.E.), and Departments of Pharmacology and Cell and Developmental Biology (C.C.H.),..."}]},{"@id":"https://cir.nii.ac.jp/crid/1383388846196935558","@type":"Researcher","foaf:name":[{"@value":"Allen J. Naftilan"}],"jpcoar:affiliationName":[{"@value":"From the Divisions of Cardiovascular Medicine (Q.S.W., J.R.B., Y.R.S., N.L.A., A.J.N., L.M., D.M.R., C.C.H.), Clinical Pharmacology (J.D.M., P.W., N.L.A., A.H.R., D.M.R.), Center for Inherited Heart Disease (Q.S.W., J.R.B., N.L.A., J.P.P., L.M., V.E., D.M.R., C.C.H.), Center for Human Genetics Research (L.D’.A.), Division of Medical Genetics and Genomic Medicine (J.P.P.), Department of Pediatric Cardiology (L.M., V.E.), and Departments of Pharmacology and Cell and Developmental Biology (C.C.H.),..."}]},{"@id":"https://cir.nii.ac.jp/crid/1383388846196935554","@type":"Researcher","foaf:name":[{"@value":"Larry Markham"}],"jpcoar:affiliationName":[{"@value":"From the Divisions of Cardiovascular Medicine (Q.S.W., J.R.B., Y.R.S., N.L.A., A.J.N., L.M., D.M.R., C.C.H.), Clinical Pharmacology (J.D.M., P.W., N.L.A., A.H.R., D.M.R.), Center for Inherited Heart Disease (Q.S.W., J.R.B., N.L.A., J.P.P., L.M., V.E., D.M.R., C.C.H.), Center for Human Genetics Research (L.D’.A.), Division of Medical Genetics and Genomic Medicine (J.P.P.), Department of Pediatric Cardiology (L.M., V.E.), and Departments of Pharmacology and Cell and Developmental Biology (C.C.H.),..."}]},{"@id":"https://cir.nii.ac.jp/crid/1383388846196935552","@type":"Researcher","foaf:name":[{"@value":"Vernat Exil"}],"jpcoar:affiliationName":[{"@value":"From the Divisions of Cardiovascular Medicine (Q.S.W., J.R.B., Y.R.S., N.L.A., A.J.N., L.M., D.M.R., C.C.H.), Clinical Pharmacology (J.D.M., P.W., N.L.A., A.H.R., D.M.R.), Center for Inherited Heart Disease (Q.S.W., J.R.B., N.L.A., J.P.P., L.M., V.E., D.M.R., C.C.H.), Center for Human Genetics Research (L.D’.A.), Division of Medical Genetics and Genomic Medicine (J.P.P.), Department of Pediatric Cardiology (L.M., V.E.), and Departments of Pharmacology and Cell and Developmental Biology (C.C.H.),..."}]},{"@id":"https://cir.nii.ac.jp/crid/1383388846196935553","@type":"Researcher","foaf:name":[{"@value":"Dan M. Roden"}],"jpcoar:affiliationName":[{"@value":"From the Divisions of Cardiovascular Medicine (Q.S.W., J.R.B., Y.R.S., N.L.A., A.J.N., L.M., D.M.R., C.C.H.), Clinical Pharmacology (J.D.M., P.W., N.L.A., A.H.R., D.M.R.), Center for Inherited Heart Disease (Q.S.W., J.R.B., N.L.A., J.P.P., L.M., V.E., D.M.R., C.C.H.), Center for Human Genetics Research (L.D’.A.), Division of Medical Genetics and Genomic Medicine (J.P.P.), Department of Pediatric Cardiology (L.M., V.E.), and Departments of Pharmacology and Cell and Developmental Biology (C.C.H.),..."}]},{"@id":"https://cir.nii.ac.jp/crid/1383388846196935424","@type":"Researcher","foaf:name":[{"@value":"Charles C. Hong"}],"jpcoar:affiliationName":[{"@value":"From the Divisions of Cardiovascular Medicine (Q.S.W., J.R.B., Y.R.S., N.L.A., A.J.N., L.M., D.M.R., C.C.H.), Clinical Pharmacology (J.D.M., P.W., N.L.A., A.H.R., D.M.R.), Center for Inherited Heart Disease (Q.S.W., J.R.B., N.L.A., J.P.P., L.M., V.E., D.M.R., C.C.H.), Center for Human Genetics Research (L.D’.A.), Division of Medical Genetics and Genomic Medicine (J.P.P.), Department of Pediatric Cardiology (L.M., V.E.), and Departments of Pharmacology and Cell and Developmental Biology (C.C.H.),..."}]}],"publication":{"publicationIdentifier":[{"@type":"PISSN","@value":"1942325X"},{"@type":"EISSN","@value":"19423268"}],"prism:publicationName":[{"@value":"Circulation: Cardiovascular Genetics"}],"dc:publisher":[{"@value":"Ovid Technologies (Wolters Kluwer Health)"}],"prism:publicationDate":"2013-08","prism:volume":"6","prism:number":"4","prism:startingPage":"317","prism:endingPage":"326"},"reviewed":"false","url":[{"@id":"https://www.ahajournals.org/doi/full/10.1161/CIRCGENETICS.113.000011"}],"createdAt":"2013-07-17","modifiedAt":"2024-05-13","relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1050011251826010368","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Alternative Splicing Regulator RBM20 and Cardiomyopathy"}]},{"@id":"https://cir.nii.ac.jp/crid/1050282677612314880","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"PRMT1 Deficiency in Mouse Juvenile Heart Induces Dilated Cardiomyopathy and Reveals Cryptic Alternative Splicing Products"}]},{"@id":"https://cir.nii.ac.jp/crid/1360013168834443520","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Gain-of-function cardiomyopathic mutations in RBM20 rewire splicing regulation and re-distribute ribonucleoprotein granules within processing bodies"}]},{"@id":"https://cir.nii.ac.jp/crid/1360576118833953664","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Pathogenic variant of RBM20 in a multiplex family with hypertrophic cardiomyopathy"}]},{"@id":"https://cir.nii.ac.jp/crid/1360861705556708992","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"I536T variant of RBM20 affects splicing of cardiac structural proteins that are causative for developing dilated cardiomyopathy"}]},{"@id":"https://cir.nii.ac.jp/crid/1361131416776377088","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"RNA sequencing reveals abnormal LDB3 splicing in sudden cardiac death"}]}],"dataSourceIdentifier":[{"@type":"CROSSREF","@value":"10.1161/circgenetics.113.000011"},{"@type":"CROSSREF","@value":"10.1016/j.isci.2018.09.023_references_DOI_1C5C1HJPtskVvXu7qNMHIRgmHsx"},{"@type":"CROSSREF","@value":"10.1038/s41467-021-26623-y_references_DOI_1C5C1HJPtskVvXu7qNMHIRgmHsx"},{"@type":"CROSSREF","@value":"10.1101/2021.06.02.446820_references_DOI_1C5C1HJPtskVvXu7qNMHIRgmHsx"},{"@type":"CROSSREF","@value":"10.3389/fmolb.2018.00105_references_DOI_1C5C1HJPtskVvXu7qNMHIRgmHsx"},{"@type":"CROSSREF","@value":"10.1016/j.forsciint.2019.109906_references_DOI_1C5C1HJPtskVvXu7qNMHIRgmHsx"},{"@type":"CROSSREF","@value":"10.1038/s41439-022-00183-z_references_DOI_1C5C1HJPtskVvXu7qNMHIRgmHsx"},{"@type":"CROSSREF","@value":"10.1007/s00109-022-02262-8_references_DOI_1C5C1HJPtskVvXu7qNMHIRgmHsx"}]}