A NEW-TYPE OF FAMILIAL CENTRAL DIABETES-INSIPIDUS CAUSED BY A SINGLE-BASE SUBSTITUTION IN THE NEUROPHYSIN-II CODING REGION OF THE VASOPRESSIN GENE

We studied the genetic basis of familial neurohypophyseal diabetes ins ipidus in a Japanese family. The members had polyuria and a deficiency of plasma vasopressin (AVP). Polymerase chain reaction (PCR) amplifie d exons of the AVP-neurophysin-II gene were subcloned and sequenced. E xons 1 and 3 were normal, but nucleotide 1884 Guanine (G) in exon 2 wa s substituted with Thymine (T), which induced a substitution of glycin e (Gly) for valine (Val). To examine the presence of this mutation in the affected subjects, we designed two mutated primers. One of them in duced a new endonuclease restriction site in the PCR fragments from no rmal, and the other induced a new endonuclease restriction site from p atients with the mutation. DNA fragments from two affected members of this family were amplified with this primer, and the PCR products were digested by endonuclease and resolved by electrophoresis. The results indicated that these subjects had both normal and mutant alleles, ind icating that the mutation was heterozygous. We concluded that this mut ation caused neurohypophyseal diabetes insipidus in this family.