부산대학교 도서관

Aims: LMNA-linked familial partial lipodystrophy type 2 (FPLD2) leads to insulin resistance-associated metabolic complications and cardiovascular diseases. We aimed to characte rise the disease phenotype in a cohort of patients carrying an LMNA founder variant. Methods: We collected clinical and biological data from patients carryi ng 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 be tween 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 patie nts 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 freque nt in patients with FPLD2 (P = 0.07). Compared to heterozygous, homozygous patients displayed more se vere lipoatrophy and metabolic alterations (lower BMI, fat mass, leptin and adiponectin, and higher trigly cerides 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 lipoatrop hy and metabolic complications. It also modulates the cardiac phenotyp e, from atherosclerosis to severe cardiomyopathy, highlighting the need for careful cardiac follow-up in affected patients. [ABSTRACT FROM AUTHOR]