AIMS LMNA-linked familial partial lipodystrophy type 2 (FPLD2) leads to insulin resistance-associated metabolic complications and cardiovascular diseases. We aimed to characterise the disease phenotype in a cohort of patients carrying an LMNA founder variant. METHODS We collected clinical and biological data from patients carrying the monoallelic or biallelic LMNA p.(Thr655Asnfs*49) variant (n = 65 and 13, respectively) and 19 non-affected relative controls followed-up in Reunion Island Lipodystrophy Competence Centre, France. RESULTS Two-thirds of patients with FPLD2 (n = 51) and one-third of controls (n = 6) displayed lipodystrophy and/or lean or android morphotype (P = 0.02). Although age and BMI were not statistically different between the two groups, the insulin resistance index (median HOMA-IR: 3.7 vs 1.5, P = 0.001), and the prevalence of diabetes, dyslipidaemia, and non-alcoholic fatty liver disease were much higher in patients with FPLD2 (51.3 vs 15.8%, 83.3 vs 42.1%, and 83.1 vs 33.3% (all P ≤ 0.01), respectively). Atherosclerosis tended to be more frequent in patients with FPLD2 (P = 0.07). Compared to heterozygous, homozygous patients displayed more severe lipoatrophy and metabolic alterations (lower BMI, fat mass, leptin and adiponectin, and higher triglycerides P ≤ 0.03) and tended to develop diabetes more frequently, and earlier (P = 0.09). Dilated cardiomyopathy and/or rhythm/conduction disturbances were the hallmark of the disease in homozygous patients, leading to death in four cases. CONCLUSIONS The level of expression of the LMNA 'Reunionese' variant determines the severity of both lipoatrophy and metabolic complications. It also modulates the cardiac phenotype, from atherosclerosis to severe cardiomyopathy, highlighting the need for careful cardiac follow-up in affected patients.

中文翻译：

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由单等位基因或双等位基因 LMNA 创始人变异引起的复发性家族性部分脂肪营养不良突出了代谢性椎板病的多方面心脏表现。

AIMS LMNA 相关的家族性部分脂肪营养不良 2 型 (FPLD2) 导致胰岛素抵抗相关的代谢并发症和心血管疾病。我们的目的是在一组携带 LMNA 创始人变体的患者中表征疾病表型。方. 结果 三分之二的 FPLD2 患者 (n = 51) 和三分之一的对照组 (n = 6) 表现出脂肪营养不良和/或瘦或机器人形态类型 (P = 0.02)。虽然两组之间的年龄和 BMI 没有统计学差异，但胰岛素抵抗指数（HOMA-IR 中位数：3.7 vs 1.5，P = 0.001），FPLD2 患者的糖尿病、血脂异常和非酒精性脂肪肝的患病率要高得多（分别为 51.3 对 15.8%、83.3 对 42.1% 和 83.1 对 33.3%（均 P ≤ 0.01））。动脉粥样硬化在 FPLD2 患者中更常见（P = 0.07）。与杂合子相比，纯合子患者表现出更严重的脂肪萎缩和代谢改变（较低的 BMI、脂肪量、瘦素和脂联素，以及较高的甘油三酯 P ≤ 0.03），并且倾向于更频繁和更早地发展为糖尿病（P = 0.09）。扩张型心肌病和/或节律/传导障碍是纯合子患者疾病的标志，导致四例死亡。结论 LMNA 'Reunionese' 变体的表达水平决定了脂肪萎缩和代谢并发症的严重程度。