{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T03:52:11Z","timestamp":1771473131866,"version":"3.50.1"},"reference-count":28,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2018,4,26]],"date-time":"2018-04-26T00:00:00Z","timestamp":1524700800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000871","name":"Mayo Clinic","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2018,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Haploinsufficiency of <jats:italic><jats:styled-content style=\"fixed-case\">TAB<\/jats:styled-content>2<\/jats:italic> is known to cause congenital heart defects and cardiomyopathy due to its important roles in cardiovascular tissue, both during development and through adult life. We report a sibling pair displaying adult\u2010onset cardiomyopathy, hypermobility, and mild myopia. Our proband, a 39\u2010year\u2010old male, presents only with the above symptoms, while his 36\u2010year\u2010old sister was also notable for a ventricular septal defect in her infancy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Whole\u2010exome sequencing was utilized to identify the molecular basis of the phenotype found in two siblings. A molecular modeling technique that takes advantage of conformational sampling advances (Maxwell's demon molecular dynamics and Monte Carlo) were used to make a model of the mutant variant for comparative analytics to the wild\u2010type.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Exome sequencing revealed a novel, heterogeneous pathogenic variant in <jats:italic><jats:styled-content style=\"fixed-case\">TAB<\/jats:styled-content>2<\/jats:italic>, c.1039 C&gt;T (p.R347X), that was present in both individuals. This pathogenic variant removes just over half the residues from the <jats:styled-content style=\"fixed-case\">TAB<\/jats:styled-content>2 protein and severely impacts its functional ability, which we describe in detail.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Analysis of the proband's family showed a history of cardiomyopathy, but no congenital heart defects or connective tissue disease. We highlight the heterogeneity in phenotype of <jats:italic><jats:styled-content style=\"fixed-case\">TAB<\/jats:styled-content>2<\/jats:italic> pathogenic variants and confirm the pathogenicity of this new variant through neoteric protein modeling techniques.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.401","type":"journal-article","created":{"date-parts":[[2018,4,27]],"date-time":"2018-04-27T04:20:10Z","timestamp":1524802810000},"page":"666-672","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Protein molecular modeling techniques investigating novel <i><scp>TAB<\/scp>2<\/i> variant R347X causing cardiomyopathy and congenital heart defects in multigenerational family"],"prefix":"10.1002","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1055-3069","authenticated-orcid":false,"given":"Thomas R.","family":"Caulfield","sequence":"first","affiliation":[{"name":"Department of Neuroscience Mayo Clinic Jacksonville FL USA"},{"name":"Mayo Graduate School Neurobiology of Disease Mayo Clinic Jacksonville FL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"suffix":"Jr.","given":"John E.","family":"Richter","sequence":"additional","affiliation":[{"name":"Department of Clinical Genomics Mayo Clinic Jacksonville FL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emily E.","family":"Brown","sequence":"additional","affiliation":[{"name":"Center for Inherited Heart Disease Johns Hopkins University Baltimore MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9167-147X","authenticated-orcid":false,"given":"Ahmed N.","family":"Mohammad","sequence":"additional","affiliation":[{"name":"Department of Clinical Genomics Mayo Clinic Jacksonville FL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel P.","family":"Judge","sequence":"additional","affiliation":[{"name":"Center for Inherited Heart Disease Johns Hopkins University Baltimore MD USA"},{"name":"Division of Cardiology Medical University of South Carolina Charleston SC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8515-744X","authenticated-orcid":false,"given":"Paldeep S.","family":"Atwal","sequence":"additional","affiliation":[{"name":"Department of Clinical Genomics Mayo Clinic Jacksonville FL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,4,26]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm301280p"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/25.17.3389"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-017-0174-z"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmgm.2011.04.005"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/prot.24131"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1155\/2011\/219515"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1003935"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1042\/BST20140321"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsb.2011.07.015"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.38254"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.15252\/embr.201540514"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22808"},{"issue":"6","key":"e_1_2_8_14_1","first-page":"525","article-title":"The PDBFINDER database: A summary of PDB, DSSP and HSSP information with added value","volume":"12","author":"Hooft R. 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