PDF(Pubmed)
Abstract：
Melanocortin 4 receptor (MC4R) mutations are the commonest cause of monogenic obesity through dysregulation of neuronal pathways in the hypothalamus and prefrontal cortex that regulate hunger and satiety. MC4R also regulates neuropathic pain pathways via JNK signaling after nerve injury. We show evidence of corneal small fiber degeneration in 2 siblings carrying a heterozygous missense variant c.508A>G, p.Ille170Val in the MC4R gene. Both children were treated with once weekly semaglutide for 6 months with no change in weight, and only a minor improvement in HbA1c and lipid profile. However, there was evidence of nerve regeneration with an increase in corneal nerve fiber density (CNFD) [child A (13.9%), child B (14.7%)], corneal nerve branch density (CNBD) [child A (110.2%), child B (58.7%)] and corneal nerve fiber length (CNFL) [child A (21.5%), child B (44.0%)].
摘要：
黑皮质素4受体（MC4R）突变是通过调节下丘脑和前额叶皮层中调节饥饿和饱腹感的神经元通路失调而导致单基因肥胖的最常见原因。MC4R还通过神经损伤后的JNK信号调节神经性疼痛途径。我们显示了2个兄弟姐妹携带杂合错义变异c.508A>G的角膜小纤维变性的证据，p.Ille170Val中的MC4R基因。两名儿童每周一次接受司马鲁肽治疗6个月，体重无变化。HbA1c和血脂谱仅有轻微改善。然而,有证据表明，随着角膜神经纤维密度（CNFD）的增加，神经再生[儿童A（13.9％），儿童B（14.7%）]，角膜神经分支密度（CNBD）[儿童A（110.2%），儿童B（58.7%）]和角膜神经纤维长度（CNFL）[儿童A（21.5%），儿童B（44.0%）]。
