3 NOVEL AVPR2 MUTATIONS IN 3 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 si ngle base deletion of one out of three guanosines (nucleotides 786-788 , 786delG) was detected. This deletion shifts the reading frame with a n altered amino acid sequence and introduces a premature stop codon (T GA) at position 270. In kindred #2 of siblings and one unrelated addit ional patient (patient #3), point mutations that change the same Pro r esidue at codon 322 in the seventh transmembrane domain to either a Se r or His (P322S or P322H) were detected. This P322 residue is well con served 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 mutatio ns are heterogeneous both in Japanese and Caucasians populations.