NOVEL MUTATIONS IN THE V2 VASOPRESSIN RECEPTOR GENE IN 2 PEDIGREES WITH CONGENITAL NEPHROGENIC DIABETES-INSIPIDUS

Novel mutations in the V2 vasopressin receptor gene were identified in two Japanese pedigrees with X-linked congenital nephrogenic diabetes insipidus. The V2 receptor belongs to the family of G-protein-coupled receptors that contain seven distinct transmembrane domains, and the V 2 receptor gene is encoded by three exons. The coding regions amplifie d by polymerase chain reaction were directly sequenced. In a pedigree, one of four consecutive guanine sequences (nucleotides 528-531) in th e second exon was deleted (528delG). This deletion mutation results in a frame shift beginning at codon 154 in the second intracellular doma in and a premature termination at codon 161. In another pedigree, a mi ssense mutation (A-->G) was identified at nucleotide position 310 in t he second exon. This point mutation, H80R, changes a histidine at codo n 80 in the second transmembrane domain to an arginine that is more po sitively charged than histidine under the neutral environment. Each mu tation cosegregated with the phenotype of diabetes insipidus and suppo sed to be a cause for resistance to arginine vasopressin.