de Roux N, Young J, Misrahi M, Schaison G, Milgrom E
INSERM U135 et Laboratoire d'Hormonologie et de Biologie Moléculaire, Hôpital Bicêtre, Le Kremlin-Bicêtre, France.
J Pediatr Endocrinol Metab. 1999 Apr;12 Suppl 1:267-75.
The association of hypogonadotropic hypogonadism with anosmia defines Kallmann's syndrome. The gene of the X-linked form of this syndrome has been cloned and several mutations described. However, the relatively small number of hypogonadotropic hypogonadic patients with Kallmann's gene defects supports the hypothesis that other genes may be involved. Idiopathic hypogonadotropic hypogonadism (IHH) is not associated with anosmia. The GnRH gene was excluded as a candidate gene in IHH since no abnormality was found in several patients. The action of the GnRH is mediated through a G-protein coupled receptor present in the cell membrane of gonadotropes. The GnRH receptor was thus another candidate gene. Recently, we described the first patient with partial hypogonadotropic hypogonadism without anosmia caused by loss of function mutations of the GnRH receptor. We compare this first family with a new family presenting complete hypogonadotropic hypogonadism and a variable degree of gonadotrope deficiency in the affected kindred, and discuss genotype-phenotype correlation.
低促性腺激素性性腺功能减退与嗅觉缺失相关联，这定义了卡尔曼综合征。该综合征X连锁形式的基因已被克隆，并描述了几种突变情况。然而，具有卡尔曼基因缺陷的低促性腺激素性性腺功能减退患者数量相对较少，这支持了可能涉及其他基因的假说。特发性低促性腺激素性性腺功能减退（IHH）与嗅觉缺失无关。由于在几名患者中未发现异常，因此GnRH基因被排除在IHH的候选基因之外。GnRH的作用是通过存在于促性腺激素细胞细胞膜中的G蛋白偶联受体介导的。因此，GnRH受体是另一个候选基因。最近，我们描述了首例因GnRH受体功能丧失突变导致的无嗅觉部分低促性腺激素性性腺功能减退患者。我们将这个首个家系与一个新的家系进行比较，新的家系中受累亲属表现为完全性低促性腺激素性性腺功能减退和不同程度的促性腺激素缺乏，并讨论基因型与表型的相关性。
