Browsing by Subject "familial partial lipodystrophy"

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    A case of familial partial lipodystrophy caused by a novel lamin A/C (LMNA) mutation in exon 1 (D47N)
    (Elsevier B.V., 2016) Kutbay N.O.; Yurekli B.S.; Onay H.; Altay C.T.; Atik T.; Hekimsoy Z.; Saygili F.; Akinci B.
    Background Familial partial lipodystrophy (FPL) is a rare genetic disorder characterized by selective lack of subcutaneous fat which is associated with insulin resistant diabetes. The Dunnigan variety (FPL2) is caused by several missense mutations in the lamin A/C (LMNA) gene, most of which are typically located in exon 8 at the codon position 482. Case report Here, we report on a Turkish family with FPL2 which is caused by a novel heterozygous missense LMNA mutation in exon 1 (D47N, c.139G > A), in the rod domain of lamins A/C. Fat distribution and metabolic features of LMNA D47N mutation were similar to typical codon 482 mutation. Metabolic abnormalities were observed as a form of insulin resistant diabetes, hypertriglyceridemia, low HDL cholesterol and hepatic steatosis. There was no evidence for neuromuscular and cardiac involvement. Conclusion Although it is previously known that alterations in the rod domain of type A lamins are involved in cardiac and neuromuscular diseases, our current observation shows that exon 1 LMNA mutations may be associated with partial lipodystrophy without any cardiac and neurological abnormalities, at least at the time of the presentation. © 2015 European Federation of Internal Medicine.
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    Cardiac phenotype in familial partial lipodystrophy
    (John Wiley and Sons Inc, 2021) Eldin A.J.; Akinci B.; da Rocha A.M.; Meral R.; Simsir I.Y.; Adiyaman S.C.; Ozpelit E.; Bhave N.; Gen R.; Yurekli B.; Ozdemir Kutbay N.; Siklar Z.; Neidert A.H.; Hench R.; Tayeh M.K.; Innis J.W.; Jalife J.; Oral H.; Oral E.A.
    Objectives: LMNA 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 design: Retrospective cohort study. Methods: Clinical 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. Results: Subjects 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. Conclusions: Our 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. © 2021 John Wiley & Sons Ltd