Cardiac phenotype in familial partial lipodystrophy
dc.contributor.author | Eldin, Abdelwahab Jalal | |
dc.contributor.author | Akinci, Baris | |
dc.contributor.author | Rocha, Andre Monteiro | |
dc.contributor.author | Meral, Rasimcan | |
dc.contributor.author | Simsir, Ilgin Yildirim | |
dc.contributor.author | Adiyaman, Suleyman Cem | |
dc.contributor.author | Ozpelit, Ebru | |
dc.contributor.author | Bhave, Nicole | |
dc.contributor.author | Gen, Ramazan | |
dc.contributor.author | Yurekli, Banu | |
dc.contributor.author | Ozdemir Kutbay, Nilufer | |
dc.contributor.author | Siklar, Zeynep | |
dc.contributor.author | Neidert, Adam H. | |
dc.contributor.author | Hench, Rita | |
dc.contributor.author | Tayeh, Marwan K. | |
dc.contributor.author | Innis, Jeffrey W. | |
dc.contributor.author | Jalife, Jose | |
dc.contributor.author | Oral, Hakan | |
dc.contributor.author | Oral, Elif A. | |
dc.date.accessioned | 2021-06-02T21:08:29Z | |
dc.date.available | 2022-07-02 17:08:28 | en |
dc.date.available | 2021-06-02T21:08:29Z | |
dc.date.issued | 2021-06 | |
dc.identifier.citation | Eldin, Abdelwahab Jalal; Akinci, Baris; Rocha, Andre Monteiro; Meral, Rasimcan; Simsir, Ilgin Yildirim; Adiyaman, Suleyman Cem; Ozpelit, Ebru; Bhave, Nicole; Gen, Ramazan; Yurekli, Banu; Ozdemir Kutbay, Nilufer; Siklar, Zeynep; Neidert, Adam H.; Hench, Rita; Tayeh, Marwan K.; Innis, Jeffrey W.; Jalife, Jose; Oral, Hakan; Oral, Elif A. (2021). "Cardiac phenotype in familial partial lipodystrophy." Clinical Endocrinology (6): 1043-1053. | |
dc.identifier.issn | 0300-0664 | |
dc.identifier.issn | 1365-2265 | |
dc.identifier.uri | https://hdl.handle.net/2027.42/167817 | |
dc.description.abstract | ObjectivesLMNA variants have been previously associated with cardiac abnormalities independent of lipodystrophy. We aimed to assess cardiac impact of familial partial lipodystrophy (FPLD) to understand the role of laminopathy in cardiac manifestations.Study designRetrospective cohort study.MethodsClinical data from 122 patients (age range: 13–77, 101 females) with FPLD were analysed. Mature human induced pluripotent stem cell‐derived cardiomyocytes (hiPSC‐CMs) from a patient with an LMNA variant were studied as proof‐of‐concept for future studies.ResultsSubjects with LMNA variants had a higher prevalence of overall cardiac events than others. The likelihood of having an arrhythmia was significantly higher in patients with LMNA variants (OR: 3.77, 95% CI: 1.45–9.83). These patients were at higher risk for atrial fibrillation or flutter (OR: 5.78, 95% CI: 1.04–32.16). The time to the first arrhythmia was significantly shorter in the LMNA group, with a higher HR of 3.52 (95% CI: 1.34–9.27). Non‐codon 482 LMNA variants were more likely to be associated with cardiac events (vs. 482 LMNA: OR: 4.74, 95% CI: 1.41–15.98 for arrhythmia; OR: 17.67, 95% CI: 2.45–127.68 for atrial fibrillation or flutter; OR: 5.71, 95% CI: 1.37–23.76 for conduction disease). LMNA mutant hiPSC‐CMs showed a higher frequency of spontaneous activity and shorter action potential duration. Functional syncytia of hiPSC‐CMs displayed several rhythm alterations such as early afterdepolarizations, spontaneous quiescence and spontaneous tachyarrhythmia, and significantly slower recovery in chronotropic changes induced by isoproterenol exposure.ConclusionsOur results highlight the need for vigilant cardiac monitoring in FPLD, especially in patients with LMNA variants who have an increased risk of developing cardiac arrhythmias. In addition, hiPSC‐CMs can be studied to understand the basic mechanisms for the arrhythmias in patients with lipodystrophy to understand the impact of specific mutations. | |
dc.publisher | Wiley Periodicals, Inc. | |
dc.subject.other | lipodystrophy | |
dc.subject.other | LMNA | |
dc.subject.other | conduction disease | |
dc.subject.other | arrhythmia | |
dc.subject.other | atrial fibrillation | |
dc.title | Cardiac phenotype in familial partial lipodystrophy | |
dc.type | Article | |
dc.rights.robots | IndexNoFollow | |
dc.subject.hlbsecondlevel | Internal Medicine and Specialties | |
dc.subject.hlbtoplevel | Health Sciences | |
dc.description.peerreviewed | Peer Reviewed | |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/167817/1/cen14426_am.pdf | |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/167817/2/cen14426-sup-0001-TableS1-4.pdf | |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/167817/3/cen14426.pdf | |
dc.identifier.doi | 10.1111/cen.14426 | |
dc.identifier.source | Clinical Endocrinology | |
dc.identifier.citedreference | Herron TJ. Calcium and voltage mapping in hiPSC‐CM monolayers. Cell Calcium. 2016; 59 ( 2–3 ): 84 ‐ 90. | |
dc.identifier.citedreference | Akinci B, Meral R, Oral EA. Phenotypic and genetic characteristics of lipodystrophy: pathophysiology, metabolic abnormalities, and comorbidities. Curr Diab Rep. 2018; 18 ( 12 ): 143. | |
dc.identifier.citedreference | Shackleton S, Lloyd DJ, Jackson SN, et al. LMNA, encoding lamin A/C, is mutated in partial lipodystrophy. Nat Genet. 2000; 24 ( 2 ): 153 ‐ 156. | |
dc.identifier.citedreference | Lattanzi G, Maggi L, Araujo‐Vilar D. Laminopathies. Nucleus. 2018; 9 ( 1 ): 543 ‐ 544. | |
dc.identifier.citedreference | Hegele R. LMNA mutation position predicts organ system involvement in laminopathies. Clin Genet. 2005; 68 ( 1 ): 31 ‐ 34. | |
dc.identifier.citedreference | Sylvius N, Tesson F. Lamin A/C and cardiac diseases. Curr Opin Cardiol. 2006; 21 ( 3 ): 159 ‐ 165. | |
dc.identifier.citedreference | Turk M, Wehnert M, Schroder R, Chevessier F. Multisystem disorder and limb girdle muscular dystrophy caused by LMNA p. R28W mutation. Neuromuscul Disord. 2013; 23 ( 7 ): 587 ‐ 590. | |
dc.identifier.citedreference | Garg A, Speckman RA, Bowcock AM. Multisystem dystrophy syndrome due to novel missense mutations in the amino‐terminal head and alpha‐helical rod domains of the lamin A/C gene. Am J Med. 2002; 112 ( 7 ): 549 ‐ 555. | |
dc.identifier.citedreference | Subramanyam L, Simha V, Garg A. Overlapping syndrome with familial partial lipodystrophy, Dunnigan variety and cardiomyopathy due to amino‐terminal heterozygous missense lamin A/C mutations. Clin Genet. 2010; 78 ( 1 ): 66 ‐ 73. | |
dc.identifier.citedreference | Caux F, Dubosclard E, Lascols O, et al. A new clinical condition linked to a novel mutation in lamins A and C with generalized lipoatrophy, insulin‐resistant diabetes, disseminated leukomelanodermic papules, liver steatosis, and cardiomyopathy. J Clin Endocrinol Metab. 2003; 88 ( 3 ): 1006 ‐ 1013. | |
dc.identifier.citedreference | Akinci B, Onay H, Demir T, et al. Clinical presentations, metabolic abnormalities and end‐organ complications in patients with familial partial lipodystrophy. Metabolism. 2017; 72: 109 ‐ 119. | |
dc.identifier.citedreference | Ajluni N, Meral R, Neidert AH, et al. Spectrum of disease associated with partial lipodystrophy: lessons from a trial cohort. Clin Endocrinol (Oxf). 2017; 86 ( 5 ): 698 ‐ 707. | |
dc.identifier.citedreference | Hussain I, Patni N, Ueda M, et al. A novel generalized lipodystrophy‐associated progeroid syndrome due to recurrent heterozygous LMNA p. T10I mutation. J Clin Endocrinol Metab. 2018; 103 ( 3 ): 1005 ‐ 1014. | |
dc.identifier.citedreference | Kwapich M, Lacroix D, Espiard S, et al. Cardiometabolic assessment of lamin A/C gene mutation carriers: a phenotype‐genotype correlation. Diabetes Metab. 2019; 45 ( 4 ): 382 ‐ 389. | |
dc.identifier.citedreference | Wahbi K, Ben Yaou R, Gandjbakhch E, et al. Development and validation of a new risk prediction score for life‐threatening ventricular tachyarrhythmias in laminopathies. Circulation. 2019; 140 ( 4 ): 293 ‐ 302. | |
dc.identifier.citedreference | Hegele RA. Premature atherosclerosis associated with monogenic insulin resistance. Circulation. 2001; 103 ( 18 ): 2225 ‐ 2229. | |
dc.identifier.citedreference | Hussain I, Patni N, Garg A. Lipodystrophies, dyslipidaemias and atherosclerotic cardiovascular disease. Pathology. 2019; 51 ( 2 ): 202 ‐ 212. | |
dc.identifier.citedreference | da Rocha AM, Creech J, Thonn E, Mironov S, Herron TJ. Detection of drug‐induced torsades de pointes arrhythmia mechanisms using hiPSC‐CM syncytial monolayers in a high‐throughput screening voltage sensitive dye assay. Toxicol Sci. 2020; 173 ( 2 ): 402 ‐ 415. | |
dc.identifier.citedreference | Lian X, Hsiao C, Wilson G, et al. Robust cardiomyocyte differentiation from human pluripotent stem cells via temporal modulation of canonical Wnt signaling. Proc Natl Acad Sci USA. 2012; 109 ( 27 ): E1848 ‐ 1857. | |
dc.identifier.citedreference | Herron TJ, Rocha AM, Campbell KF, et al. Extracellular matrix‐mediated maturation of human pluripotent stem cell‐derived cardiac monolayer structure and electrophysiological function. Circ Arrhythm Electrophysiol. 2016; 9 ( 4 ): e003638. | |
dc.identifier.citedreference | Jeru I, Vatier C, Vantyghem MC, Lascols O, Vigouroux C. LMNA‐associated partial lipodystrophy: anticipation of metabolic complications. J Med Genet. 2017; 54 ( 6 ): 413 ‐ 416. | |
dc.identifier.citedreference | van Rijsingen IA, Arbustini E, Elliott PM, et al. Risk factors for malignant ventricular arrhythmias in lamin a/c mutation carriers a European cohort study. J Am Coll Cardiol. 2012; 59 ( 5 ): 493 ‐ 500. | |
dc.identifier.citedreference | Kumar S, Baldinger SH, Gandjbakhch E, et al. Long‐term arrhythmic and nonarrhythmic outcomes of lamin A/C mutation carriers. J Am Coll Cardiol. 2016; 68 ( 21 ): 2299 ‐ 2307. | |
dc.identifier.citedreference | Panikkath R, Panikkath D, Sanchez‐Iglesias S, Araujo‐Vilar D, Lado‐Abeal J. An uncommon association of familial partial lipodystrophy, dilated cardiomyopathy, and conduction system disease. J Investig Med High Impact Case Rep. 2016; 4 ( 3 ): 2324709616658495. | |
dc.identifier.citedreference | van der Kooi AJ, Bonne G, Eymard B, et al. Lamin A/C mutations with lipodystrophy, cardiac abnormalities, and muscular dystrophy. Neurology. 2002; 59 ( 4 ): 620 ‐ 623. | |
dc.identifier.citedreference | Haque WA, Vuitch F, Garg A. Post‐mortem findings in familial partial lipodystrophy, Dunnigan variety. Diabet Med. 2002; 19 ( 12 ): 1022 ‐ 1025. | |
dc.identifier.citedreference | Vantyghem MC, Pigny P, Maurage CA, et al. Patients with familial partial lipodystrophy of the Dunnigan type due to a LMNA R482W mutation show muscular and cardiac abnormalities. J Clin Endocrinol Metab. 2004; 89 ( 11 ): 5337 ‐ 5346. | |
dc.identifier.citedreference | Hoorntje ET, Bollen IA, Barge‐Schaapveld DQ, et al. Lamin A/C‐related cardiac disease: late onset with a variable and mild phenotype in a large cohort of patients with the lamin A/C p. (Arg331Gln) Founder Mutation. Circ Cardiovasc Genet. 2017; 10 ( 4 ): e001631. | |
dc.identifier.citedreference | van Tintelen JP, Tio RA, Kerstjens‐Frederikse WS, et al. Severe myocardial fibrosis caused by a deletion of the 5’ end of the lamin A/C gene. J Am Coll Cardiol. 2007; 49 ( 25 ): 2430 ‐ 2439. | |
dc.identifier.citedreference | Ho R, Hegele RA. Complex effects of laminopathy mutations on nuclear structure and function. Clin Genet. 2019; 95 ( 2 ): 199 ‐ 209. | |
dc.identifier.citedreference | Bizy A, Guerrero‐Serna G, Hu B, et al. Myosin light chain 2‐based selection of human iPSC‐derived early ventricular cardiac myocytes. Stem Cell Res. 2013; 11 ( 3 ): 1335 ‐ 1347. | |
dc.identifier.citedreference | Morad M, Zhang XH. Mechanisms of spontaneous pacing: sinoatrial nodal cells, neonatal cardiomyocytes, and human stem cell derived cardiomyocytes. Can J Physiol Pharmacol. 2017; 95 ( 10 ): 1100 ‐ 1107. | |
dc.identifier.citedreference | Tang L, Joung B, Ogawa M, Chen PS, Lin SF. Intracellular calcium dynamics, shortened action potential duration, and late‐phase 3 early afterdepolarization in Langendorff‐perfused rabbit ventricles. J Cardiovasc Electrophysiol. 2012; 23 ( 12 ): 1364 ‐ 1371. | |
dc.identifier.citedreference | Rivera‐Torres J, Calvo CJ, Llach A, et al. Cardiac electrical defects in progeroid mice and Hutchinson‐Gilford progeria syndrome patients with nuclear lamina alterations. Proc Natl Acad Sci USA. 2016; 113 ( 46 ): E7250 ‐ E7259. | |
dc.working.doi | NO | en |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
Files in this item
Remediation of Harmful Language
The University of Michigan Library aims to describe library materials in a way that respects the people and communities who create, use, and are represented in our collections. Report harmful or offensive language in catalog records, finding aids, or elsewhere in our collections anonymously through our metadata feedback form. More information at Remediation of Harmful Language.
Accessibility
If you are unable to use this file in its current format, please select the Contact Us link and we can modify it to make it more accessible to you.