{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T06:14:01Z","timestamp":1788156841739,"version":"build-2803163510"},"reference-count":68,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T00:00:00Z","timestamp":1785196800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T00:00:00Z","timestamp":1785196800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Case Reports"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Desmin, a crucial intermediate filament in muscle cells, maintains structural integrity in cardiac muscle and provides stability to striated muscle cells. Mutations in the\n                    <jats:italic>DES<\/jats:italic>\n                    gene lead to desminopathies, causing diverse cardiac and skeletal myopathies. We examine an Iranian family with a highly penetrant p.Arg383His variant in the\n                    <jats:italic>DES<\/jats:italic>\n                    gene, resulting in severe hypertrophic cardiomyopathy (HCM) without skeletal phenotypes. Moreover, we discuss all reported disease\u2010causing missense variants, examining their clinical manifestations across different domains. We assessed demographic data, clinical features, and genetic analysis in members of this Iranian family. Whole genome sequencing (WGS), in silico structural and functional predictions, was also used to investigate genetic entities. Also, a mini\u2010review was performed across various databases to identify all disease\u2010causing missense variants within the\n                    <jats:italic>DES<\/jats:italic>\n                    gene. WGS identified a p.Arg383His variant in the\n                    <jats:italic>DES<\/jats:italic>\n                    gene in the Iranian family. Analyzing 119 disease\u2010causing missense variants in desmin revealed limited correlation between variant location and phenotypes. A significant prevalence (36.9%) of conduction diseases was linked to variants in various domains. Heart failure appeared enriched among variants located in coil2B, while syncope was more frequently reported in variants affecting coil2B and the tail domains; however, these observations are exploratory and literature\u2010derived. Different domains showed varying associations with specific clinical outcomes, such as spine ankylosis in the tail domain and dysphonia in the desmin head domain. The present study reports an Iranian family exhibiting severe HCM due to a likely pathogenic\n                    <jats:italic>DES<\/jats:italic>\n                    gene variant, lacking skeletal myopathy phenotypes. Also, examination of all missense variants highlighted clinical heterogeneity and complex inheritance patterns among individuals carrying different variants in the\n                    <jats:italic>DES<\/jats:italic>\n                    gene. In this context, genetic analysis is a valuable diagnostic tool for effectively managing affected patients, identifying carriers, and facilitating future family planning decisions.\n                  <\/jats:p>","DOI":"10.1002\/ccr3.73051","type":"journal-article","created":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T04:32:47Z","timestamp":1785299567000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Unveiling New Insights: Reinterpreting\n                    <scp>\n                      <i>DES<\/i>\n                    <\/scp>\n                    Mutation, p.\n                    <scp>Arg383His<\/scp>\n                    , Through a Study of an Iranian Family With Isolated Hypertrophic Cardiomyopathy, Implication for Phenotype\u2013Genotype Correlation Analysis"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6864-0149","authenticated-orcid":false,"given":"Saeideh","family":"Kavousi","sequence":"first","affiliation":[{"name":"Department of Medical Genetics, Faculty of Medical Sciences Tarbiat Modares University  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farzad","family":"Kamali","sequence":"additional","affiliation":[{"name":"Rajaie Cardiovascular Medical and Research Center Iran University of Medical Sciences  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1083-1660","authenticated-orcid":false,"given":"Bahareh","family":"Rabbani","sequence":"additional","affiliation":[{"name":"Growth and Development Research Tehran University of Medical Sciences  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehrdad","family":"Behmanesh","sequence":"additional","affiliation":[{"name":"Department of Genetics, Faculty of Biological Sciences Tarbiat Modares University  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8614-1538","authenticated-orcid":false,"given":"Nejat","family":"Mahdieh","sequence":"additional","affiliation":[{"name":"Growth and Development Research Tehran University of Medical Sciences  Tehran Iran"},{"name":"Cardiogenetic Research Center, Rajaie Cardiovascular Medical and Research Center Iran University of Medical Sciences  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehrdad","family":"Noruzinia","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Faculty of Medical Sciences Tarbiat Modares University  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,28]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1177\/03000605211006598"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s10038-017-0383-x"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes10110918"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes12010121"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2012.10.017"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2022.971501"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.2010.01512.x"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.3906\/biy-2107-54"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cjco.2021.05.003"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000012542"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2019.01375"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awm039"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2012-101487"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12551-018-0429-0"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.2169\/internalmedicine.0992-22"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2018.04.078"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/16.3.1215"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-016-0974-4"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2890"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2007-8-11-r232"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2892"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btu703"},{"key":"e_1_2_13_24_1","doi-asserted-by":"crossref","unstructured":"J.Ren Z.Li J.Yang N.Xu T.Yang andD. 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