UCP3基因新突变致非综合征性肥胖的特征分析

Characteristic Analysis of Non-Syndromic Obesity Caused by a New Mutation in the UCP3 Gene

摘要: 目的：单基因非综合征性肥胖(MNSO)是一类独立于环境因素并由单一基因突变引起的个体肥胖，明确其病因与临床特征具有重要意义。方法：患者因腰椎间盘突出在我科住院治疗，收集病史及各项检查结果，因高度肥胖行全外显子组测序，明确病因并对致病基因突变进行生物信息学分析。结果：患者自10岁开始体重明显增加，入院时体重指数(BMI) 39.81，同时合并糖尿病与高血压，经基因检测在UCP3基因的3号外显子上发现变异(c.208C>T, p.R70W)，导致UCP3蛋白的第70个氨基酸Arg被Trp替代。Mutation Taster和Revel软件均预测该基因变异具有致病性。蛋白质3D模型显示突变主要发生在缬氨酸(Val)和精氨酸(Arg)，而且UCP3基因突变还可以增加2型糖尿病的发病风险。结论：UCP3基因突变是单基因非综合征性肥胖和2型糖尿病重要遗传因素。

Abstract: Objective: Monogenic non-syndromic obesity (MNSO) is a type of individual obesity that is inde-pendent of environmental factors and caused by a single gene mutation. It is of great significance to clarify its etiology and clinical characteristics. Methods: The patients were hospitalized in our de-partment due to lumbar disc herniation. The medical history and various examination results were collected. The whole Exon group was sequenced due to high obesity. The etiology was identified and the pathogenic gene mutation was analyzed by bioinformatics. Results: The patient’s weight in-creased significantly since he was 10 years old. At admission, his body mass index (BMI) was 39.81. At the same time, he was complicated with diabetes and hypertension. Through Genetic testing, a mutation was found in exon 3 of UCP3 gene (c.208C>T, p.R70W), resulting in the replacement of Arg, the 70th amino acid of UCP3 protein, by Trp. Mutation Taster and Revel software both predict the pathogenicity of this gene variant. The protein 3D model showed that mutations mainly occurred in Valine (Val) and arginine (Arg), and UCP3 gene mutations could also increase the risk of type 2 dia-betes. Conclusions: Mutation of UCP3 is an important genetic factor for monogenic non-syndromic obesity and type 2 diabetes.