LMNA基因突变所致先天性家族性部分脂肪萎缩综合征2型的临床遗传学研究

Clinical and genetic study of iipodystrophic syndrome caused by LMNA mutation

目的通过1例脂肪萎缩综合征患者的临床特点和遗传信息来探索脂肪萎缩综合征的发病机制。方法收集2015年12月北京协和医院内分泌科收治的1例脂肪萎缩综合征患者的临床资料，并对患者进行弥散加权成像脂肪定量、瘦素和脂联素水平测定及脂肪萎缩综合征相关基因测序。结果弥散加权成像提示患者全身多处皮下脂肪萎缩；瘦素水平为0，脂联素水平为3mg／L；基因检测提示患者存在LMNA基因突变，突变位点为c．1045C〉T（p．349R〉W）。结论患者病程中出现特征性脂肪萎缩面貌、胰岛素抵抗和脂代谢紊乱等典型脂肪萎缩综合征临床特点。患者同时存在LMNA基因突变及瘦素和脂联素水平显著低下，这些因素可能在疾病的发生发展中起着重要作用。

Objective To explore the underlying pathogenic mechanism of lipodystrophic syndrome by analyzing the clinical manifestation and genetic information of a patient with lipodystrophy. Methods Clinical and laboratory data of a patient with lipodystrophy admitted to Peking Union Medical College Hospital in December 2015 were investigated. The quantification of adipose tissue was achieved by diffuse weight imaging. The levels of leptin and adiponectin were determined. Gene mutations related to congenital lipodystrophy were tested by Sanger sequencing. Results Diffuse weight imaging showed atrophy of subcutaneous adipose tissue in multiple sites of the body. The levels of leptin and adiponeetin were 0 and 3 mg/L respectively. Sanger sequencing result elicited LMNA mutation with c. 1045C〉T（p.349R〉 W）. Conclusions The patient presents with classic lipodystrophic manifestation, including characteristic lipoatrophic appearance, insulin resistance and disorder of lipid metabolism and extremely low levels of leptin and adiponectin. The LMNA mutation and the low levels of leptin and adiponectin may contribute to the pathogenesis of lipodystrophic syndrome.