{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T22:45:50Z","timestamp":1781649950704,"version":"3.54.5"},"reference-count":52,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Genomic and Precision Medicine"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:sec>\n            <jats:title>BACKGROUND:<\/jats:title>\n            <jats:p>\n              Heterozygous pathogenic variants in the central region (exon 23\u201334) of\n              <jats:italic toggle=\"yes\">FBN2<\/jats:italic>\n              cause a hereditary connective tissue disorder named congenital contractural arachnodactyly, which presents with obligatory skeletal features but rarely with vascular manifestations. Scarce data exist on the association between\n              <jats:italic toggle=\"yes\">FBN2<\/jats:italic>\n              variants and aortic disease. This study aimed to investigate whether the location of\n              <jats:italic toggle=\"yes\">FBN2<\/jats:italic>\n              variants correlates with distinct clinical features, including aortic disease.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>METHODS:<\/jats:title>\n            <jats:p>\n              In this case-controlled cohort study, we ascertained clinical features, sequenced 62 (candidate) disease genes, and classified variants according to the American College of Medical Genetics and Genomics\/Association for Molecular Pathology guidelines in 392 patients with suspected connective tissue or thoracic aortic diseases. We summarized our results and published data and compared clinical manifestations between patients with variants outside and within the central region of\n              <jats:italic toggle=\"yes\">FBN2<\/jats:italic>\n              .\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>RESULTS:<\/jats:title>\n            <jats:p>\n              Heterozygous\n              <jats:italic toggle=\"yes\">FBN2<\/jats:italic>\n              variants outside the central region were identified in 10 patients from 5 families. Two variants were of uncertain significance, 1 was likely pathogenic, and 2 were pathogenic. A total of 60% of these patients had thoracic aortic disease, but only 20% were diagnosed with congenital contractural arachnodactyly according to an established clinical scoring system. Combined data from the literature and this study revealed that patients with\n              <jats:italic toggle=\"yes\">FBN2<\/jats:italic>\n              variants outside the central region presented with aortic dilatation (55.0% versus 9.9%;\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              &lt;0.001) more often and had less pronounced musculoskeletal manifestations (congenital contractural arachnodactyly score, 5.6\u00b15.1 versus 9.8\u00b13.6;\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              =0.011) compared with those with central region variants.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>CONCLUSIONS:<\/jats:title>\n            <jats:p>\n              Our results suggest that heterozygous\n              <jats:italic toggle=\"yes\">FBN2<\/jats:italic>\n              variants outside the central region predispose individuals to thoracic aortic disease and are less associated with the typical clinical presentation of congenital contractural arachnodactyly than pathogenic variants in the\n              <jats:italic toggle=\"yes\">FBN2<\/jats:italic>\n              central region.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circgen.124.004672","type":"journal-article","created":{"date-parts":[[2025,5,23]],"date-time":"2025-05-23T06:19:26Z","timestamp":1747981166000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":4,"title":["Thoracic Aortic Disease in Patients With Heterozygous Variants Outside the Central Region of\n            <i>FBN2<\/i>"],"prefix":"10.1161","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8978-9914","authenticated-orcid":true,"given":"Till Joscha","family":"Demal","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Surgery (T.J.D., M.S., H.R., C.D.), University Heart and Vascular Center, Hamburg, Germany."},{"name":"Institute of 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G.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helke","family":"Sch\u00fcler","sequence":"additional","affiliation":[{"name":"Department of Cardiology (H.S., K.S., Y.K., M.R.), University Heart and Vascular Center, Hamburg, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katalin","family":"Sz\u00f6cs","sequence":"additional","affiliation":[{"name":"Department of Cardiology (H.S., K.S., Y.K., M.R.), University Heart and Vascular Center, Hamburg, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4449-7739","authenticated-orcid":true,"given":"Jakob","family":"Olfe","sequence":"additional","affiliation":[{"name":"Pediatric Cardiology Clinic (J.O., V.S., T.S.M.), University Heart and Vascular Center, Hamburg, 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