Recent studies reported an impact of the melanocortin 3 receptor (MC3R) on the regulation of body weight, linear growth and puberty timing. Previously, allele p.44Ile of a frequent non-synonymous variant (NSV) p.Val44Ile was reported to be associated with decreased lean body mass (LBM) and later puberty in both sexes. We Sanger sequenced the coding region of MC3R in 185 children or adolescents with short normal stature (SNS) or 258 individuals with severe obesity, and 192 healthy-lean individuals. Eleven variants (six NSVs) were identified. In-silico analyses ensued. Three rare loss-of-function (LoF) variants (p.Phe45Ser, p.Arg220Ser and p.Ile298Ser) were only found in severely obese individuals. One novel highly conserved NSV (p.Ala214Val), predicted to increase protein stability, was detected in a single lean female. In the individuals with SNS, we observed deviation from Hardy–Weinberg Equilibrium (HWE) (p = 0.012) for p.Val44Ile (MAF = 11.62%). Homozygous p.44Ile carriers with SNS had an increased BMI, but this effect did not remain significant after Bonferroni correction. In line with previous findings, the detected LoF NSVs may suggest that dysfunction in MC3R is associated with decreased body height, obesity and delayed puberty.

最近的研究报道了黑皮质素 3 受体 (MC3R) 对体重调节、线性生长和青春期时间的影响。此前，据报道，常见非同义变异 (NSV) p.Val44Ile 的等位基因 p.44Ile 与两性的去脂体重 (LBM) 减少和青春期延迟相关。我们对 185 名正常身材矮小 (SNS) 儿童或青少年或 258 名严重肥胖者以及 192 名健康瘦人的MC3R编码区进行了 Sanger 测序。已鉴定出 11 种变体（6 种 NSV）。计算机模拟随后进行了分析。三种罕见的功能丧失 (LoF) 变异（p.Phe45Ser、p.Arg220Ser 和 p.Ile298Ser）仅在严重肥胖个体中发现。在一名瘦女性身上检测到了一种新型高度保守的 NSV (p.Ala214Val)，预计可以提高蛋白质稳定性。在具有 SNS 的个体中，我们观察到 p.Val44Ile (MAF = 11.62%) 与Hardy–Weinberg 平衡 (HWE) ( p = 0.012) 的偏差。具有 SNS 的纯合 p.44Ile 携带者的 BMI 有所增加，但在 Bonferroni 校正后，这种影响不再显着。与之前的发现一致，检测到的 LoF NSV 可能表明 MC3R 功能障碍与身高下降、肥胖和青春期延迟有关。