{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T15:43:13Z","timestamp":1787240593025,"version":"build-2736575974"},"reference-count":53,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"16","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2017,10,17]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Cardiomyopathy and arrhythmias are under significant genetic influence. Here, we studied a family with dilated cardiomyopathy and associated conduction system disease in whom prior clinical cardiac gene panel testing was unrevealing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      Whole-genome sequencing and induced pluripotent stem cells were used to examine a family with dilated cardiomyopathy and atrial and ventricular arrhythmias. We also characterized a mouse model with heterozygous and homozygous deletion of\n                      <jats:italic>Mybphl<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      Whole-genome sequencing identified a premature stop codon, R255X, in the\n                      <jats:italic>MYBPHL<\/jats:italic>\n                      gene encoding MyBP-HL (myosin-binding protein-H like), a novel member of the myosin-binding protein family.\n                      <jats:italic>MYBPHL<\/jats:italic>\n                      was found to have high atrial expression with low ventricular expression. We determined that MyBP-HL protein was myofilament associated in the atria, and truncated MyBP-HL protein failed to incorporate into the myofilament. Human cell modeling demonstrated reduced expression from the mutant\n                      <jats:italic>MYBPHL<\/jats:italic>\n                      allele. Echocardiography of\n                      <jats:italic>Mybphl<\/jats:italic>\n                      heterozygous and null mouse hearts exhibited a 36% reduction in fractional shortening and an increased diastolic ventricular chamber size. Atria weight normalized to total heart weight was significantly increased in\n                      <jats:italic>Mybphl<\/jats:italic>\n                      heterozygous and null mice. Using a reporter system, we detected robust expression of\n                      <jats:italic>Mybphl<\/jats:italic>\n                      in the atria, and in discrete puncta throughout the right ventricular wall and septum, as well. Telemetric electrocardiogram recordings in\n                      <jats:italic>Mybphl<\/jats:italic>\n                      mice revealed cardiac conduction system abnormalities with aberrant atrioventricular conduction and an increased rate of arrhythmia in heterozygous and null mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>\n                      The findings of reduced ventricular function and conduction system defects in\n                      <jats:italic>Mybphl<\/jats:italic>\n                      mice support that\n                      <jats:italic>MYBPHL<\/jats:italic>\n                      truncations may increase risk for human arrhythmias and cardiomyopathy.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circulationaha.117.028585","type":"journal-article","created":{"date-parts":[[2017,8,4]],"date-time":"2017-08-04T20:40:23Z","timestamp":1501879223000},"page":"1477-1491","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":40,"title":["Experimental Modeling Supports a Role for MyBP-HL as a Novel Myofilament Component in Arrhythmia and Dilated Cardiomyopathy"],"prefix":"10.1161","volume":"136","author":[{"given":"David Y.","family":"Barefield","sequence":"first","affiliation":[{"name":"From Center for Genetic Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL (D.Y.B., M.J.P., J.U.E., M.H., L.D.-C., E.M.M.); Molecular Pathogenesis and Molecular Medicine, University of Chicago, IL (E.Y.K.); Feinberg Cardiovascular Institute, Northwestern University Feinberg School of Medicine, Chicago, IL (L.D.W.); Committee on Development, Regeneration and Stem Cell Biology, University of Chicago, IL (A.H.V.); Northwestern University Center for Advanced Molecular Imaging,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan J.","family":"Puckelwartz","sequence":"additional","affiliation":[{"name":"From Center for Genetic Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL (D.Y.B., M.J.P., J.U.E., M.H., L.D.-C., E.M.M.); Molecular Pathogenesis and Molecular Medicine, University of Chicago, IL (E.Y.K.); Feinberg Cardiovascular Institute, Northwestern University Feinberg School of Medicine, Chicago, IL (L.D.W.); Committee on Development, Regeneration and Stem Cell Biology, University of Chicago, IL (A.H.V.); Northwestern University Center for Advanced Molecular Imaging,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellis Y.","family":"Kim","sequence":"additional","affiliation":[{"name":"From Center for Genetic Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL (D.Y.B., M.J.P., J.U.E., M.H., L.D.-C., E.M.M.); Molecular Pathogenesis and Molecular Medicine, University of Chicago, IL (E.Y.K.); Feinberg Cardiovascular Institute, Northwestern University Feinberg School of Medicine, Chicago, IL (L.D.W.); Committee on Development, Regeneration and Stem Cell Biology, University of Chicago, IL (A.H.V.); Northwestern University Center for Advanced Molecular Imaging,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa D.","family":"Wilsbacher","sequence":"additional","affiliation":[{"name":"From Center for Genetic Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL (D.Y.B., M.J.P., J.U.E., M.H., L.D.-C., E.M.M.); Molecular Pathogenesis and Molecular Medicine, University of Chicago, IL (E.Y.K.); Feinberg Cardiovascular Institute, Northwestern University Feinberg School of Medicine, Chicago, IL (L.D.W.); Committee on Development, Regeneration and Stem Cell Biology, University of Chicago, IL (A.H.V.); Northwestern University Center for Advanced Molecular Imaging,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andy H.","family":"Vo","sequence":"additional","affiliation":[{"name":"From Center for Genetic Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL (D.Y.B., M.J.P., J.U.E., M.H., L.D.-C., E.M.M.); Molecular Pathogenesis and Molecular Medicine, University of Chicago, IL (E.Y.K.); Feinberg Cardiovascular Institute, Northwestern University Feinberg School of Medicine, Chicago, IL (L.D.W.); Committee on Development, Regeneration and Stem Cell Biology, University of Chicago, IL (A.H.V.); Northwestern University Center for Advanced Molecular Imaging,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily A.","family":"Waters","sequence":"additional","affiliation":[{"name":"From Center for Genetic Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL (D.Y.B., M.J.P., J.U.E., M.H., L.D.-C., E.M.M.); Molecular Pathogenesis and Molecular Medicine, University of Chicago, IL (E.Y.K.); Feinberg Cardiovascular Institute, Northwestern University Feinberg School of Medicine, Chicago, IL (L.D.W.); Committee on Development, Regeneration and Stem Cell Biology, University of Chicago, IL (A.H.V.); Northwestern University Center for Advanced Molecular Imaging,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judy U.","family":"Earley","sequence":"additional","affiliation":[{"name":"From Center for Genetic Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL (D.Y.B., M.J.P., J.U.E., M.H., L.D.-C., E.M.M.); Molecular Pathogenesis and Molecular Medicine, University of Chicago, IL (E.Y.K.); Feinberg Cardiovascular Institute, Northwestern University Feinberg School of Medicine, Chicago, IL (L.D.W.); Committee on Development, Regeneration and Stem Cell Biology, University of Chicago, IL (A.H.V.); Northwestern University Center for Advanced Molecular Imaging,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Hadhazy","sequence":"additional","affiliation":[{"name":"From Center for Genetic Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL (D.Y.B., M.J.P., J.U.E., M.H., L.D.-C., E.M.M.); Molecular Pathogenesis and Molecular Medicine, University of Chicago, IL (E.Y.K.); Feinberg Cardiovascular Institute, Northwestern University Feinberg School of Medicine, Chicago, IL (L.D.W.); Committee on Development, Regeneration and Stem Cell Biology, University of Chicago, IL (A.H.V.); Northwestern University Center for Advanced Molecular Imaging,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Dellefave-Castillo","sequence":"additional","affiliation":[{"name":"From Center for Genetic Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL (D.Y.B., M.J.P., J.U.E., M.H., L.D.-C., E.M.M.); Molecular Pathogenesis and Molecular Medicine, University of Chicago, IL (E.Y.K.); Feinberg Cardiovascular Institute, Northwestern University Feinberg School of Medicine, Chicago, IL (L.D.W.); Committee on Development, Regeneration and Stem Cell Biology, University of Chicago, IL (A.H.V.); Northwestern University Center for Advanced Molecular Imaging,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenzo L.","family":"Pesce","sequence":"additional","affiliation":[{"name":"From Center for Genetic Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL (D.Y.B., M.J.P., J.U.E., M.H., L.D.-C., E.M.M.); Molecular Pathogenesis and Molecular Medicine, University of Chicago, IL (E.Y.K.); Feinberg Cardiovascular Institute, Northwestern University Feinberg School of Medicine, Chicago, IL (L.D.W.); Committee on Development, Regeneration and Stem Cell Biology, University of Chicago, IL (A.H.V.); Northwestern University Center for Advanced Molecular Imaging,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth M.","family":"McNally","sequence":"additional","affiliation":[{"name":"From Center for Genetic Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL (D.Y.B., M.J.P., J.U.E., M.H., L.D.-C., E.M.M.); Molecular Pathogenesis and Molecular Medicine, University of Chicago, IL (E.Y.K.); Feinberg Cardiovascular Institute, Northwestern University Feinberg School of Medicine, Chicago, IL (L.D.W.); Committee on Development, Regeneration and Stem Cell Biology, University of Chicago, IL (A.H.V.); Northwestern University Center for Advanced Molecular Imaging,..."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.106.174287"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2015.01.013"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardfail.2012.01.013"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1110186"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1295-434"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1295-438"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.309"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.108.838672"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2014.11.018"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2008.09.070"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCGENETICS.113.000448"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btu071"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.4161\/fly.19695"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth0410-248"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1101\/gr.3577405"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2653"},{"key":"e_1_3_4_18_2","unstructured":"ClinVar https:\/\/www.ncbi.nlm.nih.gov\/clinvar\/. 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