Mutations in genes encoding proteins located in the leptin/melanocortin pathway have been identified in the rare cases of genetic obesities. Heterozygous variants of MRAP2, encoding a G coupled-protein receptor accessory protein implicated in energy control notably via the melanocortin-4 receptor, have been recently identified. A 24-year-old patient with early-onset severe obesity (body mass index [BMI]: 64 kg/m2) associated with hypertension, respiratory complications, nonalcoholic fatty liver disease, and type 2 diabetes was referred to our department. Sleeve gastrectomy was successful. A new heterozygous variant in MRAP2 (NM_138409.4: c.154G>C/p.G52R) variant was identified in the patient DNA. Functional assessment confirmed that this new variant was pathogenic. We report a new pathogenic loss-of-function mutation in MRAP2 in a patient suffering from a severe multicomplicated obesity. This confirms the metabolic phenotype in patients with this monogenic form of obesity. Longer follow-up will be necessary. Our finding will allow a personalized medicine.

中文翻译：

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减肥手术成功的肥胖患者中 MRAP2 的一种新致病性变异。

在罕见的遗传性肥胖病例中，已经发现了编码位于瘦素/黑皮质素通路中的蛋白质的基因突变。最近已鉴定出 MRAP2 的杂合变体，编码 G 偶联蛋白受体辅助蛋白，特别是通过黑皮质素 4 受体参与能量控制。一名24岁的患者，患有早发性严重肥胖（体重指数[BMI]：64 kg/m2），伴有高血压、呼吸系统并发症、非酒精性脂肪肝和2型糖尿病，转诊至我科。袖状胃切除术成功。在患者 DNA 中鉴定出 MRAP2 中的新杂合变异体 (NM_138409.4: c.154G>C/p.G52R)。功能评估证实这种新变异具有致病性。我们报告了一位患有严重多发性肥胖症的患者中 MRAP2 的一种新的致病性功能丧失突变。这证实了这种单基因肥胖症患者的代谢表型。需要更长时间的随访。我们的发现将允许个体化医疗。