{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T21:50:54Z","timestamp":1788558654996,"version":"build-2803163510"},"reference-count":57,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2018,2,6]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              Genetic causes of dilated cardiomyopathy (DCM) are incompletely understood. LRRC10 (leucine\u2010rich repeat\u2013containing 10) is a cardiac\u2010specific protein of unknown function. Heterozygous mutations in\n              <jats:italic>LRRC10<\/jats:italic>\n              have been suggested to cause DCM, and deletion of\n              <jats:italic>Lrrc10<\/jats:italic>\n              in mice results in DCM.\n            <\/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              Whole\u2010exome sequencing was carried out on a patient who presented at 6\u00a0weeks of age with DCM and her unaffected parents, filtering for rare, deleterious, recessive, and de novo variants. Whole\u2010exome sequencing followed by trio\u2010based filtering identified a homozygous recessive variant in\n              <jats:italic>LRRC10<\/jats:italic>\n              , I195T. Coexpression of I195T\n              <jats:italic>LRRC10<\/jats:italic>\n              with the L\u2010type Ca\n              <jats:sup>2+<\/jats:sup>\n              channel (Ca\n              <jats:sub>v<\/jats:sub>\n              1.2, \u03b2\n              <jats:sub>2CN2<\/jats:sub>\n              , and \u03b1\n              <jats:sub>2<\/jats:sub>\n              \u03b4 subunits) in HEK293 cells resulted in a significant \u22480.5\u2010fold decrease in I\n              <jats:sub>Ca,L<\/jats:sub>\n              at 0\u00a0mV, in contrast to the \u22481.4\u2010fold increase in I\n              <jats:sub>Ca,L<\/jats:sub>\n              by coexpression of\n              <jats:italic>LRRC10<\/jats:italic>\n              (n=9\u201312,\n              <jats:italic>P<\/jats:italic>\n              &lt;0.05). Coexpression of\n              <jats:italic>LRRC10<\/jats:italic>\n              or I195T\n              <jats:italic>LRRC10<\/jats:italic>\n              did not alter the surface membrane expression of Ca\n              <jats:sub>v<\/jats:sub>\n              1.2.\n              <jats:italic>LRRC10<\/jats:italic>\n              coexpression with Ca\n              <jats:sub>v<\/jats:sub>\n              1.2 in the absence of auxiliary \u03b2\n              <jats:sub>2CN2<\/jats:sub>\n              and \u03b1\n              <jats:sub>2<\/jats:sub>\n              \u03b4 subunits revealed coassociation of Ca\n              <jats:sub>v<\/jats:sub>\n              1.2 and LRRC10 and a hyperpolarizing shift in the voltage dependence of activation (n=6\u20139,\n              <jats:italic>P<\/jats:italic>\n              &lt;0.05). Ventricular myocytes from\n              <jats:italic>Lrrc10<\/jats:italic>\n              <jats:sup>\n                <jats:italic>\u2212\/\u2212<\/jats:italic>\n              <\/jats:sup>\n              mice had significantly smaller I\n              <jats:sub>Ca,L<\/jats:sub>\n              , and coimmunoprecipitation experiments confirmed association between LRRC10 and the Ca\n              <jats:sub>v<\/jats:sub>\n              1.2 subunit in mouse hearts.\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              Examination of a patient with DCM revealed homozygosity for a previously unreported\n              <jats:italic>LRRC10<\/jats:italic>\n              variant: I195T. Wild\u2010type and I195T LRRC10 function as cardiac\u2010specific subunits of L\u2010type Ca\n              <jats:sup>2+<\/jats:sup>\n              channels and exert dramatically different effects on channel gating, providing a potential link to DCM.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.117.006428","type":"journal-article","created":{"date-parts":[[2018,2,8]],"date-time":"2018-02-08T09:47:33Z","timestamp":1518083253000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":17,"title":["Pediatric Dilated Cardiomyopathy\u2010Associated\n            <i>LRRC10<\/i>\n            (Leucine\u2010Rich Repeat\u2013Containing 10) Variant Reveals LRRC10 as an Auxiliary Subunit of Cardiac L\u2010Type Ca\n            <sup>2+<\/sup>\n            Channels"],"prefix":"10.1161","volume":"7","author":[{"given":"Marites T.","family":"Woon","sequence":"first","affiliation":[{"name":"Cellular and Molecular Arrhythmia Research Program, University of Wisconsin\u2010Madison, Madison, WI"},{"name":"Department of Medicine, University of Wisconsin\u2010Madison, Madison, WI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pamela A.","family":"Long","sequence":"additional","affiliation":[{"name":"Mayo Graduate School, Molecular Pharmacology and Experimental Therapeutics Track, Mayo Clinic, Rochester, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise","family":"Reilly","sequence":"additional","affiliation":[{"name":"Cellular and Molecular Arrhythmia Research Program, University of Wisconsin\u2010Madison, Madison, WI"},{"name":"Department of Medicine, University of Wisconsin\u2010Madison, Madison, WI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jared M.","family":"Evans","sequence":"additional","affiliation":[{"name":"Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexis M.","family":"Keefe","sequence":"additional","affiliation":[{"name":"Cellular and Molecular Arrhythmia Research Program, University of Wisconsin\u2010Madison, Madison, WI"},{"name":"Department of Medicine, University of Wisconsin\u2010Madison, Madison, WI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin R.","family":"Lea","sequence":"additional","affiliation":[{"name":"Cellular and Molecular Arrhythmia Research Program, University of Wisconsin\u2010Madison, Madison, WI"},{"name":"Department of Medicine, University of Wisconsin\u2010Madison, Madison, WI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carl J.","family":"Beglinger","sequence":"additional","affiliation":[{"name":"Cellular and Molecular Arrhythmia Research Program, University of Wisconsin\u2010Madison, Madison, WI"},{"name":"Department of Medicine, University of Wisconsin\u2010Madison, Madison, WI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ravi C.","family":"Balijepalli","sequence":"additional","affiliation":[{"name":"Cellular and Molecular Arrhythmia Research Program, University of Wisconsin\u2010Madison, Madison, WI"},{"name":"Department of Medicine, University of Wisconsin\u2010Madison, Madison, WI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youngsook","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Cell and Regenerative Biology, University of Wisconsin\u2010Madison, Madison, WI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy M.","family":"Olson","sequence":"additional","affiliation":[{"name":"Division of Pediatric Cardiology, Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, MN"},{"name":"Division of Cardiovascular Diseases, Department of Internal Medicine, Mayo Clinic, Rochester, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy J.","family":"Kamp","sequence":"additional","affiliation":[{"name":"Cellular and Molecular Arrhythmia Research Program, University of Wisconsin\u2010Madison, Madison, WI"},{"name":"Department of Cell and Regenerative Biology, University of Wisconsin\u2010Madison, Madison, WI"},{"name":"Department of Medicine, University of Wisconsin\u2010Madison, Madison, 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