{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T17:17:55Z","timestamp":1783012675492,"version":"3.54.6"},"reference-count":17,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T00:00:00Z","timestamp":1775174400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T00:00:00Z","timestamp":1775174400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["K08HL179262"],"award-info":[{"award-number":["K08HL179262"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["25CDA1438764"],"award-info":[{"award-number":["25CDA1438764"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Autosomal recessive loss\u2010of\u2010function variants in\n                    <jats:italic>PPP1R13L<\/jats:italic>\n                    cause an ultra\u2010rare cardiocutaneous syndrome characterized by rapidly progressive arrhythmogenic cardiomyopathy (ACM).\n                    <jats:italic>PPP1R13L<\/jats:italic>\n                    encodes iASPP, which has two potentially overlapping mechanisms driving ACM as both a regulator of NF\u03baB\u2010mediated inflammation and a binding partner within the cardiac desmosome. This study explores immunotherapy and the underlying pathophysiology in two pediatric cases. Two patients (aged 47 and 32\u2009months) with biallelic\n                    <jats:italic>PPP1R13L<\/jats:italic>\n                    variants presented with refractory ventricular arrhythmias and heart failure. Both received IL\u20101 blockade as adjunct therapy. Explanted heart tissue was analyzed via quantitative immunofluorescent microscopy to assess NF\u03ba\u03b2 nuclear localization and desmin localization at the intercalated disks (ID). IL\u20101 blockade was associated with reduced ventricular ectopy and normalized serum cytokine levels (IL\u20101, IL\u201010) but without contractile recovery. Histology analysis revealed increased NF\u03ba\u03b2 signaling only in non\u2010cardiomyocytes but with loss of desmin at the ID in\n                    <jats:italic>PPP1R13L<\/jats:italic>\n                    cardiomyopathy compared to non\u2010\n                    <jats:italic>PPP1R13L<\/jats:italic>\n                    dilated cardiomyopathy controls.\n                    <jats:italic>PPP1R13L<\/jats:italic>\n                    cardiomyopathy involves systemic inflammation, but loss of desmin\u2010desmosome anchoring in cardiomyocytes appears to be the central mechanism of\n                    <jats:italic>PPP1R13L<\/jats:italic>\n                    cardiomyopathy. Targeted IL\u20101 blockade can be considered as adjunctive therapy for patients with\n                    <jats:italic>PPP1R13L<\/jats:italic>\n                    cardiomyopathy but further studies on treatments directed at the underlying mechanism are needed.\n                  <\/jats:p>","DOI":"10.1002\/ajmg.a.70156","type":"journal-article","created":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T07:06:36Z","timestamp":1775199996000},"page":"1807-1813","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Targeted Anti\u2010\n                    <scp>IL<\/scp>\n                    \u20101 Immunomodulatory Therapy in Pediatric Onset\n                    <i>PPP1R13L<\/i>\n                    \u2010Related Arrhythmogenic Cardiomyopathy"],"prefix":"10.1002","volume":"200","author":[{"given":"Aaron","family":"Renberg","sequence":"first","affiliation":[{"name":"Division of Cardiology, Department of Internal Medicine University of Michigan  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Savannah","family":"Coppersmith","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Internal Medicine University of Michigan  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Owen","family":"Merritt","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Internal Medicine University of Michigan  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amer","family":"Heider","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Michigan  Ann Arbor USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Helms","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Internal Medicine University of Michigan  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8919-5243","authenticated-orcid":false,"given":"Thomas","family":"Michniacki","sequence":"additional","affiliation":[{"name":"Division of Pediatric Hematology\/Oncology, Department of Pediatrics University of Michigan  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7366-6143","authenticated-orcid":false,"given":"Jack","family":"Luxford","sequence":"additional","affiliation":[{"name":"Heart Centre for Children, The Children's Hospital at Westmead  Sydney Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Josephi\u2010Taylor","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, The Children's Hospital at Westmead  Sydney 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