title: Autosomal dominant neurohypophyseal diabetes insipidus in a Swiss family, caused by a novel mutation (C59Delta/A60W) in the neurophysin moiety of prepro-vasopressin-neurophysin II (AVP-NP II).
abstract: OBJECTIVE
  To study clinical, morphological and molecular characteristics in a Swiss family with autosomal dominant familial neurohypophyseal diabetes insipidus (adFNDI).
  
  
  METHODS
  A 15-month-old girl presenting with symptoms of polydipsia and polyuria was investigated by water deprivation test. Evaluation of the family revealed three further family members with symptomatic vasopressin-deficient diabetes insipidus. T1-weighted magnetic resonance images of the posterior pituitary were taken in two affected adult family members and molecular genetic analysis was performed in all affected individuals.
  
  
  RESULTS
  The water deprivation test in the 15-month-old child confirmed the diagnosis of vasopressin-deficient diabetes insipidus and the pedigree was consistent with autosomal dominant inheritance. The characteristic bright spot of the normal vasopressin-containing neurophypophysis was absent in both adults with adFNDI. Direct sequence analysis revealed a new deletion (177-179DeltaCGC) in exon 2 of the AVP-NP II gene in all affected individuals. At the amino acid level, this deletion eliminates cysteine 59 (C59Delta) and substitutes alanine 60 by tryptophan (A60W) in the AVP-NP II precursor; interestingly, the remainder of the reading frame remains unchanged. According to the three-dimensional structure of neurophysin, C59 is involved in a disulphide bond with C65.
  
  
  CONCLUSIONS
  Deletion of C59 and substitution of A60W in the AVP-NP II precursor is predicted to disrupt one of the seven disulphide bridges required for correct folding of the neurophysin moiety and thus disturb the function of neurophysin as the vasopressin transport protein. These data are in line with the clinical and morphological findings in the reported family with adFNDI.
authors.affiliation: Department of Paediatric Endocrinology, Diabetology and Metabolism, University Children's Hospital, 3010 Bern, Switzerland.
authors.forename: C E
authors.initials: CE
authors.lastname: Flück
authors.forename: J
authors.initials: J
authors.lastname: Deladoëy
authors.forename: S
authors.initials: S
authors.lastname: Nayak
authors.forename: O
authors.initials: O
authors.lastname: Zeller
authors.forename: P
authors.initials: P
authors.lastname: Kopp
authors.forename: P E
authors.initials: PE
authors.lastname: Mullis
mesh_terms: D000595:Amino Acid Sequence / Q000235:genetics; D001127:Arginine Vasopressin / Q000172:deficiency*; D001483:Base Sequence / Q000235:genetics; D003919:Diabetes Insipidus / Q000175:diagnosis / Q000209:etiology* / Q000235:genetics*; D005260:Female; D005799:Genes, Dominant; D006801:Humans; D007223:Infant; D008279:Magnetic Resonance Imaging; D008967:Molecular Biology / Q000379:methods; D008969:Molecular Sequence Data; D009481:Neurophysins / Q000235:genetics*; D010375:Pedigree; D011498:Protein Precursors / Q000235:genetics*; D013557:Switzerland; D014667:Vasopressins / Q000235:genetics*
chemical_list: C438657:AVP protein, human; D009481:Neurophysins; D011498:Protein Precursors; D014667:Vasopressins; D001127:Arginine Vasopressin