A novel arginine vasopressin-neurophysin II mutation causes autosomal dominant neurohypophyseal diabetes insipidus and morphologic pituitary changes.

To determine the genetic basis of autosomal dominant neurohypophyseal diabetes insipidus (ADNDI) in a Cypriot family, we ascertained and studied a large, four-generation kindred in which all participating family members had arginine vasopressin-neurophysin II (AVP-NP-II) gene analyses done. A G to A transition was found by DNA sequence analysis at position 1773 (G1773A) of the AVP-NPII gene which is predicted to encode a substitution of tyrosine for cysteine in codon 59 (CYS59TYR). The mutation was confirmed by restriction endonuclease analysis of PCR amplification products that contain the corresponding segment of the AVP-NPII gene. To clarify the morphologic status of the pituitaries of family members, 12 affected and 3 nonaffected members had magnetic resonance imaging (MRI) studies. The bright spot of the posterior pituitary lobe was completely absent in 75% and faintly identified in 25% of the affected members who were examined with MRI. We conclude that (1) a novel G1773A transition in exon 2 of the AVP-NPII gene causes ADNDI in the large Cypriot kindred studied, (2) this mutation is predicted to encode a CYS59TYR substitution in NPII, and (3) MRI studies of the posterior pituitary lobes of affected family members show either a decreased intensity or a complete absence of the bright spot in all cases studied.