Tajima T, Nakae J, Takekoshi Y, Takahashi Y, Yuri K, Nagashima T, Fujieda K
Department of Pediatrics, Hokkaido University School of Medicine, Sapporo, Japan.
Pediatr Res. 1996 Mar;39(3):522-6. doi: 10.1203/00006450-199603000-00022.
We identified three novel mutations of the arginine vasopressin (AVP) V2 receptor (AVPR2) gene in Japanese families with X-linked congenital nephrogenic diabetes insipidus (NDI). In kindred #1 of siblings, a single base deletion of one out of three guanosines (nucleotides 786-788, 786delG) was detected. This deletion shifts the reading frame with an altered amino acid sequence and introduces a premature stop codon (TGA) at position 270. In kindred #2 of siblings and one unrelated additional patient (patient #3), point mutations that change the same Pro residue at codon 322 in the seventh transmembrane domain to either a Ser or His (P322S or P322H) were detected. This P322 residue is well conserved among rat V1 and V2 receptors, the human oxytocin receptor, and other G protein-coupled receptors, and is thought to be important for proper insertion of the receptor into the membrane. The AVPR2 mutations are heterogeneous both in Japanese and Caucasians populations.
我们在患有X连锁先天性肾性尿崩症（NDI）的日本家族中鉴定出精氨酸加压素（AVP）V2受体（AVPR2）基因的三种新突变。在同胞家族#1中，检测到三个鸟苷中的一个鸟苷单碱基缺失（核苷酸786 - 788，786delG）。这种缺失改变了阅读框，导致氨基酸序列改变，并在第270位引入了一个提前终止密码子（TGA）。在同胞家族#2和另一名无亲缘关系的患者（患者#3）中，检测到点突变，该突变将第七跨膜结构域中第322位密码子的同一个脯氨酸残基分别改变为丝氨酸或组氨酸（P322S或P322H）。这个P322残基在大鼠V1和V₂受体、人催产素受体以及其他G蛋白偶联受体中高度保守，并且被认为对于受体正确插入膜中很重要。AVPR2突变在日本人和高加索人群中都是异质性的。
