Bichet D G, Arthus M F, Lonergan M, Hendy G N, Paradis A J, Fujiwara T M, Morgan K, Gregory M C, Rosenthal W, Didwania A
Unité de Recherche Clinique, Hôpital du Sacré-Coeur, Montréal, Québec, Canada.
J Clin Invest. 1993 Sep;92(3):1262-8. doi: 10.1172/JCI116698.
In X-linked nephrogenic diabetes insipidus (NDI) the urine of male patients is not concentrated after the administration of the antidiuretic hormone arginine-vasopressin. This disease is due to mutations in the V2 receptor gene that maps to chromosome region Xq28. In 1969, Bode and Crawford suggested that most NDI patients in North America shared common ancestors of Ulster Scot immigrants who arrived in Halifax in 1761 on the ship Hopewell. A link between this family and a large Utah kindred was also suggested. DNA was obtained from 17 affected male patients from the "Hopewell" kindred and from four additional families from Nova Scotia and New Brunswick who shared the same Xq28 NDI haplotype. The Utah kindred and two families (Q2, Q3) from Quebec were also studied. The "Hopewell" mutation, W71X, is a single base substitution (G-->A) that changes codon 71 from TGG (tryptophan) to TGA (stop). The W71X mutation was found in affected members of the Hopewell and of the four satellite families. The W71X mutation is the cause of X-linked NDI for the largest number of related male patients living in North America. Other families (Utah, Q2 and Q3) that are historically and ethnically unrelated bear other mutations in the V2 receptor gene.
在X连锁肾性尿崩症（NDI）中，男性患者在使用抗利尿激素精氨酸加压素后尿液仍不能浓缩。这种疾病是由定位于X染色体Xq28区域的V2受体基因突变引起的。1969年，博德和克劳福德提出，北美大多数NDI患者拥有阿尔斯特苏格兰移民的共同祖先，这些移民于1761年乘坐“希望号”船抵达哈利法克斯。还提出了这个家族与犹他州一个大家族之间的联系。从“希望号”家族的17名受影响男性患者以及新斯科舍省和新不伦瑞克省另外四个共享相同Xq28 NDI单倍型的家族中获取了DNA。还对犹他州家族以及魁北克的两个家族（Q2、Q3）进行了研究。“希望号”突变W71X是一个单碱基替换（G→A），它将密码子71从TGG（色氨酸）变为TGA（终止密码子）。在“希望号”家族以及四个卫星家族的受影响成员中发现了W71X突变。W71X突变是北美大量相关男性患者X连锁NDI的病因。其他在历史和种族上无关的家族（犹他州、Q2和Q3）在V2受体基因中存在其他突变。
