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Abstract：
Berardinelli-Seip congenital lipoatrophy (BSCL) is characterized by near total fat atrophy, associated with the progressive development of metabolic complications. BSCL type 1 (BSCL1) is caused by mutations in AGPAT2, encoding 1-acylglycerol-3phosphate-O-acyltransferase β (recently renamed lysophosphatidic acid acyltransferase beta), which catalyzes the transformation of lysophosphatidic acid in phosphatidic acid, the precursor of glycerophospholipids and triglycerides. BSCL1 is an autosomal recessive disease due to AGPAT2 pathogenic variants leading to a depletion of triglycerides inside the adipose organ, and to a defective signaling of key elements involved in proper adipogenesis. We herein investigated the characteristics of two AGPAT2 variants in Caucasian Italian patients with Berardinelli-Seip congenital lipoatrophy. The first patient exhibited a novel homozygous nonsense c.430 C > T AGPAT2 mutation (p.Gln144*) predicting the synthesis of a truncated enzyme of approximately half of the proper size. The second patient harbored a homozygous AGPAT2 missense variant (p.Arg159Cys), never described previously in BSCL1 patients: the segregation of the disease with the mutation in the pedigree of the family and the in silico analysis are compatible with a causative role of the p.Arg159Cys variant. We remark that BSCL1 can be clinically very heterogeneous at presentation and that the associated complications, occurring in the natural history of the disease, reduce life-expectancy. We point to the necessity for medical treatments capable of reducing the risk of cardiovascular death. In BSCL1 patients, the assessment of cardiovascular disease with conventional diagnostic means maybe particularly challenging.
摘要：
Berardinelli-Seip先天性脂肪萎缩（BSCL）的特征是几乎全部脂肪萎缩，与代谢并发症的进行性发展有关。BSCL1型（BSCL1）是由AGPAT2中的突变引起的，编码1-酰基甘油-3磷酸-O-酰基转移酶β（最近更名为溶血磷脂酸酰基转移酶β），催化溶血磷脂酸在磷脂酸中的转化，甘油磷脂和甘油三酯的前体。BSCL1是一种常染色体隐性遗传疾病，由于AGPAT2致病变异导致脂肪器官内甘油三酯的消耗，以及与正常脂肪形成有关的关键元素的信号传导缺陷。我们在此研究了两种AGPAT2变体在意大利白种人Berardinelli-Seip先天性脂肪萎缩患者中的特征。第一位患者表现出一种新的纯合无义c.430C>TAGPAT2突变（p。Gln144*）预测大约适当大小的一半的截短酶的合成。第二名患者具有纯合AGPAT2错义变体（p。Arg159Cys)，以前从未在BSCL1患者中描述过：在家族系谱中突变的疾病分离和计算机模拟分析与p.Arg159Cys变异的致病作用是一致的。我们注意到BSCL1在临床上可能非常异质，并且相关的并发症，发生在疾病的自然史上，减少预期寿命。我们指出有必要进行能够降低心血管死亡风险的药物治疗。在BSCL1患者中，用常规诊断手段评估心血管疾病可能特别具有挑战性.
