Boson W L, Della Manna T, Damiani D, Miranda D M, Gadelha M R, Liberman B, Correa H, Romano-Silva M A, Friedman E, Silva F F, Ribeiro P A, De Marco L
Department of Pharmacology, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
Genet Test. 2006 Fall;10(3):157-62. doi: 10.1089/gte.2006.10.157.
Nephrogenic diabetes insipidus (NDI) is an inherited disorder characterized by renal resistance to the antidiuretic effect of arginine vasopressin (AVP), resulting in polyuria, polydipsia, and hypoosmolar urine. In the vast majority of cases, NDI is associated with germ-line mutations in the vasopressin receptor type 2 gene (AVPR2) and in about 8% of the cases with the water channel aquaporin-2 gene (AQP-2) mutations. To date, approximately 277 families with 185 germ-line mutations in the AVPR2 gene have been described worldwide. In the present study, the AVPR2 gene was genotyped in eight unrelated Brazilian kindred with NDI. In five of these NDI families, novel mutations were noted (S54R, I130L, S187R, 219delT, and R230P), whereas three seemingly unrelated probands were found to harbor previously described AVPR2 gene mutations (R106C, R137H, R337X). Additionally a novel polymorphism (V281V) was detected. In conclusion, although NDI is a rare disease, the findings of mutations scattered over the entire coding region of the AVPR2 gene are a valuable model to determine structure function relationship in G-protein-coupled receptor related diseases. Furthermore, our data indicate that in Brazil the spectrum of AVPR2 gene mutations is "family specific".
肾性尿崩症（NDI）是一种遗传性疾病，其特征为肾脏对精氨酸加压素（AVP）的抗利尿作用产生抵抗，导致多尿、烦渴和低渗尿。在绝大多数情况下，NDI与2型加压素受体基因（AVPR2）的种系突变相关，约8%的病例与水通道蛋白-2基因（AQP-2）突变有关。迄今为止，全球已描述了约277个家族，其AVPR2基因存在185种种系突变。在本研究中，对8个不相关的巴西NDI家系进行了AVPR2基因分型。在其中5个NDI家族中，发现了新的突变（S54R、I130L、S187R、219delT和R230P），而3个看似不相关的先证者被发现携带先前描述的AVPR2基因突变（R106C、R137H、R337X）。此外，还检测到一种新的多态性（V281V）。总之，尽管NDI是一种罕见疾病，但在AVPR2基因整个编码区域分散发现的突变是确定G蛋白偶联受体相关疾病结构功能关系的宝贵模型。此外，我们的数据表明，在巴西，AVPR2基因突变谱具有“家族特异性”。
