Hutchins B Ian, Kotan L Damla, Taylor-Burds Carol, Ozkan Yusuf, Cheng Paul J, Gurbuz Fatih, Tiong Jean D R, Mengen Eda, Yuksel Bilgin, Topaloglu A Kemal, Wray Susan
National Institute of Neurological Disorders and Stroke (B.I.H., C.T.-B., P.J.C., J.D.R.T., S.W.), National Institutes of Health, Bethesda, Maryland 20892; Department of Biotechnology (L.D.K., A.K.T.), Institute of Sciences, Cukurova University, 01330 Adana, Turkey; Fırat University (Y.O.), 23119 Elazıg, Turkey; and Division of Pediatric Endocrinology (F.G., E.M., B.Y., A.K.T.), Faculty of Medicine, Cukurova University, 01330 Adana, Turkey.
Endocrinology. 2016 May;157(5):1956-66. doi: 10.1210/en.2015-1846. Epub 2016 Mar 25.
The first mutation in a gene associated with a neuronal migration disorder was identified in patients with Kallmann Syndrome, characterized by hypogonadotropic hypogonadism and anosmia. This pathophysiological association results from a defect in the development of the GnRH and the olfactory system. A recent genetic screening of Kallmann Syndrome patients revealed a novel mutation in CCDC141. Little is known about CCDC141, which encodes a coiled-coil domain containing protein. Here, we show that Ccdc141 is expressed in GnRH neurons and olfactory fibers and that knockdown of Ccdc141 reduces GnRH neuronal migration. Our findings in human patients and mouse models predict that CCDC141 takes part in embryonic migration of GnRH neurons enabling them to form a hypothalamic neuronal network to initiate pulsatile GnRH secretion and reproductive function.
在卡尔曼综合征患者中发现了与神经元迁移障碍相关基因的首个突变，该综合征的特征为促性腺激素缺乏性性腺功能减退和嗅觉缺失。这种病理生理关联源于促性腺激素释放激素（GnRH）和嗅觉系统发育缺陷。最近对卡尔曼综合征患者的基因筛查发现了CCDC141基因的一个新突变。人们对CCDC141知之甚少，它编码一种含有卷曲螺旋结构域的蛋白质。在此，我们表明Ccdc141在GnRH神经元和嗅觉纤维中表达，并且敲低Ccdc141会减少GnRH神经元的迁移。我们在人类患者和小鼠模型中的研究结果预测，CCDC141参与GnRH神经元的胚胎迁移，使其能够形成下丘脑神经元网络以启动GnRH的脉冲式分泌和生殖功能。
