title: Identification of 13 new mutations in the vasopressin-neurophysin II gene in 17 kindreds with familial autosomal dominant neurohypophyseal diabetes insipidus.
abstract: Familial neurohypophyseal diabetes insipidus (FNDI) is an autosomal dominant disorder characterized by progressive postnatal deficiency of arginine vasopressin as a result of mutation in the gene that encodes the hormone. To determine the extent of mutations in the coding region that produce the phenotype, we studied members of 17 unrelated kindreds with the disorder. We sequenced all 3 exons of the gene by using a rapid, direct dye-terminator method and found the causative mutation in each kindred. In four kindreds, the mutations were each identical to mutations described in other affected families. In the other 13 kindreds each mutation was unique. There were two missense mutations that altered the cleavage region of the signal peptide, seven missense mutations in exon 2, which codes for the conserved portion of the protein, one nonsense mutation in exon 2, and three nonsense mutations in exon 3. These findings, together with the clinical features of FNDI, suggest that each of the mutations exerts an effect by directing the production of a pre-prohormone that cannot be folded, processed, or degraded properly and eventually destroys vasopressinergic neurons.
authors.affiliation: Research Laboratory of Nephrology and Hypertension, Skejby Hospital, Aarhus University, Denmark.
authors.forename: S
authors.initials: S
authors.lastname: Rittig
authors.forename: G L
authors.initials: GL
authors.lastname: Robertson
authors.forename: C
authors.initials: C
authors.lastname: Siggaard
authors.forename: L
authors.initials: L
authors.lastname: Kovács
authors.forename: N
authors.initials: N
authors.lastname: Gregersen
authors.forename: J
authors.initials: J
authors.lastname: Nyborg
authors.forename: E B
authors.initials: EB
authors.lastname: Pedersen
mesh_terms: D001127:Arginine Vasopressin / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D001483:Base Sequence; D017931:DNA Primers; D003919:Diabetes Insipidus / Q000235:genetics*; D005091:Exons; D005260:Female; D005799:Genes, Dominant; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009481:Neurophysins / Q000235:genetics*; D009690:Nucleic Acid Conformation; D010375:Pedigree; D010904:Pituitary Gland, Posterior; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011498:Protein Precursors / Q000235:genetics; D017433:Protein Structure, Secondary; D015183:Restriction Mapping; D017384:Sequence Deletion; D013728:Terminator Regions, Genetic
chemical_list: D017931:DNA Primers; D009481:Neurophysins; D011498:Protein Precursors; D001127:Arginine Vasopressin