{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T19:48:42Z","timestamp":1778960922365,"version":"3.51.4"},"reference-count":21,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2024,3,5]],"date-time":"2024-03-05T00:00:00Z","timestamp":1709596800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCDD"],"abstract":"<jats:p>Mutations in the LMNA-gene can cause a variety of \u2018laminopathies\u2019. These laminopathies are associated with a range of phenotypes, including disorders affecting the adipose tissue, peripheral nerves, the heart, such as dilated cardiomyopathy and conduction system abnormalities, and less commonly, progeroid disorders. This case series describes two families in which two novel LMNA-gene variants were identified, and who presented with an atypical progeroid phenotype with primarily premature aortic and mitral valve stenosis. Interestingly, these families exhibited no clear evidence of multisystem involvement, illustrating the complex role of lamins A\/C.<\/jats:p>","DOI":"10.3390\/jcdd11030086","type":"journal-article","created":{"date-parts":[[2024,3,5]],"date-time":"2024-03-05T03:03:20Z","timestamp":1709607800000},"page":"86","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Atypical Progeria Primarily Manifesting as Premature Cardiac Valvular Disease Segregates with LMNA-Gene Variants"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7280-8258","authenticated-orcid":false,"given":"Hoi W.","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Cardiology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6268-3404","authenticated-orcid":false,"given":"Ivo P.","family":"Van de Peppel","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julie W.","family":"Rutten","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3246-8359","authenticated-orcid":false,"given":"J. Wouter","family":"Jukema","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands"},{"name":"Netherlands Heart Institute, 3511 EP Utrecht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-5086-1595","authenticated-orcid":false,"given":"Emmelien","family":"Aten","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ingrid M.","family":"Jazet","sequence":"additional","affiliation":[{"name":"Department of General Internal Medicine and Endocrinology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-9632-6713","authenticated-orcid":false,"given":"Tamara T.","family":"Koopmann","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4461-4293","authenticated-orcid":false,"given":"Daniela Q. C. M.","family":"Barge-Schaapveld","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7208-5769","authenticated-orcid":false,"given":"Nina","family":"Ajmone Marsan","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1146\/annurev-pathol-042220-034240","article-title":"Molecular Pathology of Laminopathies","volume":"17","author":"Shin","year":"2022","journal-title":"Annu. Rev. Pathol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1136\/heartjnl-2017-312338","article-title":"Lamin and the heart","volume":"104","author":"Captur","year":"2018","journal-title":"Heart"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1016\/j.ehj.2004.03.007","article-title":"Often seen but rarely recognised: Cardiac complications of lamin A\/C mutations","volume":"25","author":"Duboc","year":"2004","journal-title":"Eur. Heart J."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1715","DOI":"10.1056\/NEJM199912023412302","article-title":"Missense mutations in the rod domain of the lamin A\/C gene as causes of dilated cardiomyopathy and conduction-system disease","volume":"341","author":"Fatkin","year":"1999","journal-title":"N. Engl. J. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1007\/s00109-004-0589-1","article-title":"Meta-analysis of clinical characteristics of 299 carriers of LMNA gene mutations: Do lamin A\/C mutations portend a high risk of sudden death?","volume":"83","author":"Bonne","year":"2005","journal-title":"J. Mol. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1007\/s00418-016-1411-1","article-title":"Molecular insights into the premature aging disease progeria","volume":"145","author":"Vidak","year":"2016","journal-title":"Histochem. Cell Biol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"101073","DOI":"10.1016\/j.arr.2020.101073","article-title":"Lamin A involvement in ageing processes","volume":"62","author":"Cenni","year":"2020","journal-title":"Ageing Res. Rev."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"5645","DOI":"10.1007\/s11033-014-3434-9","article-title":"Genetic predisposition to calcific aortic stenosis and mitral annular calcification","volume":"41","author":"Kutikhin","year":"2014","journal-title":"Mol. Biol. Rep."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2941","DOI":"10.1016\/j.jacc.2017.04.051","article-title":"Association of Triglyceride-Related Genetic Variants With Mitral Annular Calcification","volume":"69","author":"Afshar","year":"2017","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2881","DOI":"10.1002\/ajmg.a.35557","article-title":"An inherited LMNA gene mutation in atypical Progeria syndrome","volume":"158","author":"Doubaj","year":"2012","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e576","DOI":"10.1016\/j.ejmg.2011.06.012","article-title":"LMNA mutation in progeroid syndrome in association with strokes","volume":"54","author":"Delgadillo","year":"2011","journal-title":"Eur. J. Med. Genet."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1055\/s-0035-1557377","article-title":"Novel LMNA mutation in a patient with progeroid phenotype","volume":"5","author":"Lehwald","year":"2007","journal-title":"J. Pediatr. Neurol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1038\/nature01629","article-title":"Recurrent de novo point mutations in lamin A cause Hutchinson-Gilford progeria syndrome","volume":"423","author":"Eriksson","year":"2003","journal-title":"Nature"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"27879","DOI":"10.1038\/srep27879","article-title":"Significance of 1B and 2B domains in modulating elastic properties of lamin A","volume":"6","author":"Bera","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2816","DOI":"10.1093\/hmg\/ddm238","article-title":"Nesprin-1 and -2 are involved in the pathogenesis of Emery Dreifuss muscular dystrophy and are critical for nuclear envelope integrity","volume":"16","author":"Zhang","year":"2007","journal-title":"Hum. Mol. Genet."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1038\/jhg.2011.65","article-title":"Novel and recurrent EMD mutations in patients with Emery-Dreifuss muscular dystrophy, identify exon 2 as a mutation hot spot","volume":"56","author":"Brown","year":"2011","journal-title":"J. Hum. Genet."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1002","DOI":"10.1038\/ejhg.2013.258","article-title":"New ZMPSTE24 (FACE1) mutations in patients affected with restrictive dermopathy or related progeroid syndromes and mutation update","volume":"22","author":"Navarro","year":"2014","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Marian, A.J. (2017). Non-syndromic cardiac progeria in a patient with the rare pathogenic p.Asp300Asn variant in the LMNA gene. BMC Med. Genet., 18.","DOI":"10.1186\/s12881-017-0480-x"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.1111\/1346-8138.12657","article-title":"First Japanese case of atypical progeroid syndrome\/atypical Werner syndrome with heterozygous LMNA mutation","volume":"41","author":"Motegi","year":"2014","journal-title":"J. Dermatol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2246310","DOI":"10.1080\/19491034.2023.2246310","article-title":"Interdependent changes of nuclear lamins, nuclear pore complexes, and ploidy regulate cellular regeneration and stress response in the heart","volume":"14","author":"Li","year":"2023","journal-title":"Nucleus"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Perepelina, K., Klauzen, P., Kostareva, A., and Malashicheva, A. (2019). Tissue-Specific Influence of Lamin A Mutations on Notch Signaling and Osteogenic Phenotype of Primary Human Mesenchymal Cells. Cells, 8.","DOI":"10.3390\/cells8030266"}],"container-title":["Journal of Cardiovascular Development and Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2308-3425\/11\/3\/86\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:09:15Z","timestamp":1760105355000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2308-3425\/11\/3\/86"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,5]]},"references-count":21,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2024,3]]}},"alternative-id":["jcdd11030086"],"URL":"https:\/\/doi.org\/10.3390\/jcdd11030086","relation":{},"ISSN":["2308-3425"],"issn-type":[{"value":"2308-3425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,5]]}}}