{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T19:48:41Z","timestamp":1778960921661,"version":"3.51.4"},"reference-count":83,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2013,5,10]],"date-time":"2013-05-10T00:00:00Z","timestamp":1368144000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2013,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:label\/><jats:p>Hutchinson\u2013Gilford Progeria Syndrome (HGPS) is a premature aging disorder caused by mutations in <jats:italic>LMNA<\/jats:italic>, which encodes the nuclear scaffold proteins lamin A and C. In HGPS and related progerias, processing of prelamin A is blocked at a critical step mediated by the zinc metalloprotease ZMPSTE24. <jats:italic>LMNA<\/jats:italic>\u2010linked progerias can be grouped into two classes: (1) the processing\u2010deficient, early onset \u201ctypical\u201d progerias (e.g., HGPS), and (2) the processing\u2010proficient \u201catypical\u201d progeria syndromes (APS) that are later in onset. Here we describe a previously unrecognized progeria syndrome with prominent cutaneous and cardiovascular manifestations belonging to the second class. We suggest the name <jats:italic>LMNA<\/jats:italic>\u2010associated cardiocutaneous progeria syndrome (LCPS) for this disorder. Affected patients are normal at birth but undergo progressive cutaneous changes in childhood and die in middle age of cardiovascular complications, including accelerated atherosclerosis, calcific valve disease, and cardiomyopathy. In addition, the proband demonstrated cancer susceptibility, a phenotype rarely described for <jats:italic>LMNA<\/jats:italic>\u2010based progeria disorders. The <jats:italic>LMNA<\/jats:italic> mutation that caused LCPS in this family is a heterozygous c.899A&gt;G (p.D300G) mutation predicted to alter the coiled\u2013coil domain of lamin A\/C. In skin fibroblasts isolated from the proband, the processing and levels of lamin A and C are normal. However, nuclear morphology is aberrant and rescued by treatment with farnesyltransferase inhibitors, as is also the case for HGPS and other laminopathies. Our findings advance knowledge of human <jats:italic>LMNA<\/jats:italic> progeria syndromes, and raise the possibility that typical and atypical progerias may converge upon a common mechanism to cause premature aging disease. \u00a9 2013 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.35971","type":"journal-article","created":{"date-parts":[[2013,5,10]],"date-time":"2013-05-10T18:42:38Z","timestamp":1368211358000},"page":"1599-1611","source":"Crossref","is-referenced-by-count":25,"title":["<i>LMNA<\/i>\u2010associated cardiocutaneous progeria: An inherited autosomal dominant premature aging syndrome with late onset"],"prefix":"10.1002","volume":"161","author":[{"given":"Megan S.","family":"Kane","sequence":"first","affiliation":[{"name":"Department of Cell Biology Johns Hopkins University School of Medicine Baltimore Maryland"},{"name":"McKusick\u2010Nathans Institute of Genetic Medicine Johns Hopkins University School of Medicine Baltimore Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark E.","family":"Lindsay","sequence":"additional","affiliation":[{"name":"Division of Pediatric Cardiology Johns Hopkins University School of Medicine Baltimore Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel P.","family":"Judge","sequence":"additional","affiliation":[{"name":"Division of Cardiology Johns Hopkins University School of Medicine Baltimore Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jemima","family":"Barrowman","sequence":"additional","affiliation":[{"name":"Department of Cell Biology Johns Hopkins University School of Medicine Baltimore Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Colette","family":"Ap Rhys","sequence":"additional","affiliation":[{"name":"McKusick\u2010Nathans Institute of Genetic Medicine Johns Hopkins University School of Medicine Baltimore Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisa","family":"Simonson","sequence":"additional","affiliation":[{"name":"Department of Medicine Johns Hopkins University School of Medicine Baltimore Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Harry C.","family":"Dietz","sequence":"additional","affiliation":[{"name":"McKusick\u2010Nathans Institute of Genetic Medicine Johns Hopkins University School of Medicine Baltimore Maryland"},{"name":"Howard Hughes Medical Institute Baltimore Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susan","family":"Michaelis","sequence":"additional","affiliation":[{"name":"Department of Cell Biology Johns Hopkins University School of Medicine Baltimore Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2013,5,10]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature11632"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/323560a0"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2012.77"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1515\/BC.2009.080"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E08-07-0704"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0032120"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/dds233"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1042\/BST20110670"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2010.05.032"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2944"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tig.2012.06.001"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2010.10.014"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10038-003-0025-3"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddi158"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0506001102"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2002-021506"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(03)14069-X"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.01.059"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2003.015651"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-genom-082908-150150"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1084125"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1652708"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1101\/sqb.2010.75.018"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20315"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2011-12-5-222"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.35557"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature01629"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.35732"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.86.1.59"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2009-0472"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/1098-1004(200102)17:2<154::AID-HUMU11>3.0.CO;2-R"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddi326"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.4103\/0974-2069.84670"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.31346"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2004.03.029"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2010.08.013"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.34336"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/0470093765.ch13"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2005.10.011"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2005.10.018"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2005-0939"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.229102"},{"key":"e_1_2_6_44_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.15.6.481"},{"key":"e_1_2_6_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.20359"},{"key":"e_1_2_6_46_1","doi-asserted-by":"publisher","DOI":"10.4161\/nucl.2.3.15731"},{"key":"e_1_2_6_47_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1651-2227.2009.01324.x"},{"key":"e_1_2_6_48_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.03263"},{"key":"e_1_2_6_49_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.33018"},{"key":"e_1_2_6_50_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0503712102"},{"key":"e_1_2_6_51_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.138032.112"},{"key":"e_1_2_6_52_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.32627"},{"key":"e_1_2_6_53_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0706898"},{"key":"e_1_2_6_54_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200802155"},{"key":"e_1_2_6_55_1","doi-asserted-by":"publisher","DOI":"10.1590\/S0004-27302008000800008"},{"key":"e_1_2_6_56_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.0022-202X.2005.23846.x"},{"key":"e_1_2_6_57_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI29042"},{"key":"e_1_2_6_58_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddi159"},{"key":"e_1_2_6_59_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02704113"},{"key":"e_1_2_6_60_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1971"},{"key":"e_1_2_6_61_1","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.M111.008094"},{"key":"e_1_2_6_62_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00395-008-0748-6"},{"key":"e_1_2_6_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbiomech.2008.08.024"},{"key":"e_1_2_6_64_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2004.019661"},{"key":"e_1_2_6_65_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1582-4934.2008.00676.x"},{"key":"e_1_2_6_66_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.32331"},{"key":"e_1_2_6_67_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.108.531780"},{"key":"e_1_2_6_68_1","first-page":"S883","article-title":"Phenotypic plasticity of LMNA mutations in cardiovascular system includes isolated cardia progeria, dilated and hypertrophic cardiomyopathies, atrial fibrillation, conduction defects and degenerative valvular diseases","volume":"118","author":"Rodriguez G","year":"2008","journal-title":"Circulation"},{"key":"e_1_2_6_69_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00246-010-9711-z"},{"key":"e_1_2_6_70_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1708"},{"key":"e_1_2_6_71_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.31803"},{"key":"e_1_2_6_72_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1735208"},{"key":"e_1_2_6_73_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0505767102"},{"key":"e_1_2_6_74_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2005-1297"},{"key":"e_1_2_6_75_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1786"},{"key":"e_1_2_6_76_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddl172"},{"key":"e_1_2_6_77_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1474-9726.2008.00382.x"},{"key":"e_1_2_6_78_1","doi-asserted-by":"publisher","DOI":"10.1002\/0470093765.ch11"},{"key":"e_1_2_6_79_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(03)14760-5"},{"key":"e_1_2_6_80_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2007.03.028"},{"key":"e_1_2_6_81_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI37679"},{"key":"e_1_2_6_82_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M708138200"},{"key":"e_1_2_6_83_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M002808"},{"key":"e_1_2_6_84_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.32259"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fajmg.a.35971","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.35971","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ajmg.a.35971","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.35971","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,18]],"date-time":"2023-10-18T07:53:58Z","timestamp":1697615638000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.35971"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,5,10]]},"references-count":83,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2013,7]]}},"alternative-id":["10.1002\/ajmg.a.35971"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.35971","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,5,10]]}}}