O'Neill M J, Tridjaja B, Smith M J, Bell K M, Warne G L, Sinclair A H
Dept. of Paediatrics & Centre for Hormone Research University of Melbourne, Royal Children's Hospital Parkville, Victoria, Australia.
Hum Mutat. 1998;11(4):340-2.
Kallmann syndrome is an inherited disease which is characterised by anosmia (inability to smell) and hypogonadotropic hypogonadism both of which are thought to occur as a result of a failure of correct neuronal migration. To date the only genetic lesions identified are mutations in the X-linked gene, KAL. We conducted a mutation screen of the KAL gene in a family with Kallmann syndrome. This identified a new mutation in the KAL gene which removed an acceptor site at the junction of exon 6/intron 5. Exon 6 of the KAL gene encodes the C-terminal portion of a fibronectin type III domain may be involved in axonal pathfinding. We presume that the described mutation would result in the removal of exon 6 resulting in a frame shift which terminates the protein prematurely. It has been proposed that both mental illness and vesico-ureteric reflux are associated with mutations in the KAL gene. However, results from the family presented here do not show an association between either trait and the KAL gene mutation.
卡尔曼综合征是一种遗传性疾病，其特征为嗅觉缺失（无法嗅觉）和低促性腺激素性性腺功能减退，这两种情况被认为是由于正确的神经元迁移失败所致。迄今为止，唯一确定的基因损伤是X连锁基因KAL中的突变。我们对一个患有卡尔曼综合征的家族进行了KAL基因的突变筛查。这确定了KAL基因中的一个新突变，该突变去除了外显子6/内含子5交界处的一个剪接受体位点。KAL基因的外显子6编码纤连蛋白III型结构域的C末端部分，可能参与轴突导向。我们推测所描述的突变会导致外显子6缺失，从而导致移码，使蛋白质过早终止。有人提出精神疾病和膀胱输尿管反流都与KAL基因突变有关。然而，这里呈现的家族研究结果并未显示出这两种特征与KAL基因突变之间存在关联。
