{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T09:30:07Z","timestamp":1776763807257,"version":"3.51.2"},"reference-count":98,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"22","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2022,11,15]]},"abstract":"<jats:sec sec-type=\"background\" xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">Dilated cardiomyopathy (DCM), characterized by progressive left ventricular enlargement and systolic dysfunction, is the most common type of cardiomyopathy and a leading cause of heart failure and cardiac death. Accumulating evidence underscores the critical role of genetic defects in the pathogenesis of DCM, and &gt;250 genes have been implicated in DCM to date. However, DCM is of substantial genetic heterogeneity, and the genetic basis underpinning DCM remains elusive in most cases.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              By genome\u2010wide scan with microsatellite markers and genetic linkage analysis in a 4\u2010generation family inflicted with autosomal\u2010dominant DCM, a new locus for DCM was mapped on chromosome 15q13.1\u2013q13.3, a 4.77\u2010cM (\u22483.43\u2009Mbp) interval between markers D15S1019 and D15S1010, with the largest 2\u2010point logarithm of odds score of 5.1175 for the marker D15S165 at recombination fraction (\u03b8)=0.00. Whole\u2010exome sequencing analyses revealed that within the mapping chromosomal region, only the mutation in the\n              <jats:italic>KLF13<\/jats:italic>\n              gene, c.430G&gt;T (p.E144X), cosegregated with DCM in the family. In addition, sequencing analyses of\n              <jats:italic>KLF13<\/jats:italic>\n              in another cohort of 266 unrelated patients with DCM and their available family members unveiled 2 new mutations, c.580G&gt;T (p.E194X) and c.595T&gt;C (p.C199R), which cosegregated with DCM in 2 families, respectively. The 3 mutations were absent from 418 healthy subjects. Functional assays demonstrated that the 3 mutants had no transactivation on the target genes\n              <jats:italic>ACTC1<\/jats:italic>\n              and\n              <jats:italic>MYH7<\/jats:italic>\n              (2 genes causally linked to DCM), alone or together with GATA4 (another gene contributing to DCM), and a diminished ability to bind the promoters of\n              <jats:italic>ACTC1<\/jats:italic>\n              and\n              <jats:italic>MYH7<\/jats:italic>\n              . Add, the E144X\u2010mutant KLF13 showed a defect in intracellular distribution.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              This investigation indicates\n              <jats:italic>KLF13<\/jats:italic>\n              as a new gene predisposing to DCM, which adds novel insight to the molecular pathogenesis underlying DCM, implying potential implications for prenatal prevention and precision treatment of DCM in a subset of patients.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.122.027578","type":"journal-article","created":{"date-parts":[[2022,11,8]],"date-time":"2022-11-08T12:05:55Z","timestamp":1667909155000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":15,"title":["KLF13 Loss\u2010of\u2010Function Mutations Underlying Familial Dilated 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