A Molecular Genetic Study of X-Linked Nephrogenic Diabetes lnspidusl

= Abstract = X-linked nephrogenic diabetes insipidus (NOI) is a rare disease characterized by absent vasopressin V2 receptor responses. Recently, the vasopressin V2 receptor gene (AVPR2 gene) was cloned, and several mutations have been reported in association with NO!. We analyzed the AVPR2 gene in a family with X-linked NO!. Genomic DNA was isolated from peripheral blood samples from 11 members of the family. Four overlapping segments covering the entire coding sequence of the AVPR2 gene were amplified by polymerase chain reaction (PCR) with the genomic DNA And DNA sequencing was done after subcloning of the PCR products into a plasmid vector. We found a mutation in the AVPR2 gene, common in 4 symptomatic male patients in the family. It was a novel missense point mutation at the codon 219 CTG to CCG resulting a transition of leucine-219, located in the 5th transmembrane domain of the receptor molecule, to proline. The T to C transition generated a new recognition site for a restriction enzyme Sma I. And 3 heterozygous female carriers of the mutant gene were detected by the pattern of Sma I digestion of PCR products including the mutation site. These results provided a strong evidence for that the mutation was the cause of NOI in this family.