Three novel AVPR2 mutations in three Japanese families with X-linked nephrogenic diabetes insipidus.

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.