title: A novel arginine vasopressin-neurophysin II mutation causes autosomal dominant neurohypophyseal diabetes insipidus and morphologic pituitary changes.
abstract: 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.
authors.affiliation: Department of Paediatrics, Arch. Makarios III Hospital, Nicosia, Cyprus. nskordis@cytanet.com.cy
authors.forename: N
authors.initials: N
authors.lastname: Skordis
authors.forename: P C
authors.initials: PC
authors.lastname: Patsalis
authors.forename: J A
authors.initials: JA
authors.lastname: Hettinger
authors.forename: M
authors.initials: M
authors.lastname: Kontou
authors.forename: E
authors.initials: E
authors.lastname: Herakleous
authors.forename: M R
authors.initials: MR
authors.lastname: Krishnamani
authors.forename: J A
authors.initials: JA
authors.lastname: Phillips
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D001127:Arginine Vasopressin / Q000235:genetics*; D002648:Child; D004247:DNA / Q000235:genetics; D003919:Diabetes Insipidus / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D005799:Genes, Dominant; D006801:Humans; D008279:Magnetic Resonance Imaging; D008875:Middle Aged; D009154:Mutation / Q000502:physiology*; D009481:Neurophysins / Q000235:genetics*; D010375:Pedigree; D010902:Pituitary Gland / Q000473:pathology*; D010904:Pituitary Gland, Posterior / Q000503:physiopathology*
chemical_list: D009481:Neurophysins; D001127:Arginine Vasopressin; D004247:DNA