A Null mutation in the vasopressin V2 receptor gene (AVPR2) associated with nephrogenic diabetes insipidus in the Hopewell kindred.
A Null mutation in the vasopressin V2 receptor gene (AVPR2) associated with nephrogenic diabetes insipidus in the Hopewell kindred.
复制标题
加压素 V2 受体基因 (AVPR2) 的空突变与霍普威尔家族中的肾性尿崩症相关。
DOI：
10.1093/hmg/2.8.1201
复制
发表时间：
1993
影响因子：
3.5
通讯作者：
Ausiello,DA
中科院分区：
文献类型：
--
作者：
Holtzman,EJ;KolakowskiJr,LF;O'Brien,D;Crawford,JD;Ausiello,DA
先天性肾源性尿崩症(DIR)是一种罕见的X连锁遗传性疾病，肾脏集合管对精氨酸加压素无反应，因此尿液对血浆持续低张。最近，V2受体基因(AVPR2)与DIR的相关性已被证实。我们已经确定了一个患有CNDI的北美大家庭中来自三代的四个家庭成员的基因序列，他们最初是用于阐明Hopewell假说的研究的一部分。有人提出，一个单一的DIR基因缺陷是由1761年抵达霍普韦尔号的阿尔斯特苏格兰人家族的一名成员引入北美的。对AVPR2的DNA测序发现，在受影响的患者中，G→A存在一个单碱基颠换，将色氨酸71改变为停止密码子。这种点突变会导致受体截断，导致等位基因基本上为零。这些数据和其他最近描述的北美家系AVPR2突变，来自阿尔斯特苏格兰人的祖先和其他来源，使得霍普韦尔假说中提出的创始人效应的断言无效。
Congenital nephrogenic diabetes insipidus (DIR) Is a rare X-linked hereditary disorder in which the renal collecting duct Is unresponsive to arginine vasopressin; thus, the urine is consistently hypotonic to plasma. Recently, the association between the V2 receptor gene (AVPR2) and DIR has been proven. We have determined the gene sequence of four family members, from three generations, of a large North American family with CNDI who were originally part of the study used to formulate theHopewellhypothesis. It had been proposed that a single DIR gene defect was Introduced to North America by a member of an Ulster Scot kindred arriving on the shipHopewellIn 1761. DNA sequencing of the AVPR2 has Identified a single base transversion from G→A which changes tryptophan 71 to a stop codon in affected patients. This point mutation causes a truncation of the receptor leading to an essentially null allele. These data and other recently described mutations in the AVPR2 In North American pedigrees, descended from Ulster Scot ancestors and other origins, make the assertion of a founder effect proposed In theHopewellhypothesis Invalid.