Contiguous gene deletion involving L1CAM and AVPR2 causes X-linked hydrocephalus with nephrogenic diabetes insipidus
Contiguous gene deletion involving L1CAM and AVPR2 causes X-linked hydrocephalus with nephrogenic diabetes insipidus
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DOI：
10.1002/ajmg.a.31536
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发表时间：
2007-03-15
影响因子：
2
通讯作者：
Hatchwell, Eli
中科院分区：
文献类型：
--
作者：
Tegay, David H.;Lane, Andrew H.;Hatchwell, Eli
x连锁脑积水伴导水管狭窄（HSAS）是由L1细胞粘附分子基因（LICAM）在Xq28位点突变或缺失引起的。中枢性尿崩症（CDI）可由脑积水引起的下丘脑功能障碍引起，必须通过外源性抗利尿激素反应与肾源性尿崩症（NDI）区分。NDI的病因是异质性的，包括精氨酸抗利尿激素受体2基因（AVPR2）的突变或缺失，该基因位于与l7cam相似的29 kb端粒上。我们确定了一位同时患有HSAS和NDI的患者，其中DNA测序失败提示可能存在连续基因缺失。证实了L1CAM内含子1到AVPR2外显子2的32.7 kb缺失。鉴定出一个90 bp的连接插入片段与侧翼序列具有短的直接重复同源性。据我们所知，这是首次报道涉及L1CAM和AVPR2的Xq28微缺失病例，定义了一种由HSAS和NDI组成的新的连续基因综合征。连续基因缺失应该被认为是所有脑积水和NDL患者的发病机制。(c) 2007 Wiley-Liss, Inc。
X-linked hydrocephalus with aqueductal stenosis (HSAS) is caused by mutation or deletion of the L1 cell adhesion molecule gene (LICAM at Xq28. Central diabetes insipidus (CDI) can arise as a consequence of resultant hypothalamic dysfunction from hydrocephalus and must be distinguished from nephrogenic diabetes insipidus (NDI) by exogenous vasopressin response. Causes of NDI are heterogeneous and include mutation or deletion of the arginine vasopressin receptor 2 gene (AVPR2), which is located similar to 29 kb telomeric to L 7 CAM. We identified a patient with both HSAS and NDI where DNA Sequencing failure suggested the possibility of a contiguous gene deletion. A 32.7 kb deletion mapping front L1CAM intron1 to AVPR2 exon2 was confirmed. A 90 bp junctional insertion fragment sharing short direct repeat homology with flanking sequences was identified. To our knowledge this is the first reported case of an Xq28 microdeletion involving both L1CAM and AVPR2, defining a new contiguous gene syndrome comprised of HSAS and NDI. Contiguous gene deletion should be considered as a mechanism for all patients presenting with hydrocephalus and NDL. (c) 2007 Wiley-Liss, Inc.