title: Autosomal dominant neurohypophyseal diabetes insipidus in two families. Molecular analysis of the vasopressin-neurophysin II gene and functional studies of three missense mutations.
abstract: BACKGROUND
  Autosomal dominant familial neurohypophyseal diabetes insipidus (adFNDI) is a rare disease with symptoms of polydipsia, polyuria and dehydration caused by arginine vasopressin deficiency. Disease onset is within infancy or adolescence. A variety of disease-causing mutations of the arginine vasopressin neurophysin II gene (AVP) on chromosome 20p13 have been described.
  
  
  METHODS
  Two Polish families with adFNDI were screened for mutations. Processing of wild-type (WT) and mutant AVP was monitored using immunocytochemical methods in stably transfected Neuro2A cells. AVP secretion into the cell culture supernatant was investigated with an enzyme immunoassay.
  
  
  RESULTS
  In the first family a heterozygous p.G96D mutation was identified. Some patients additionally carried a novel heterozygous mutation p.A159T. The second family presented with a heterozygous mutation p.C98G. Confocal laser microscopy unveiled accumulation of p.G96D and p.C98G prohormones in the cellular bodies, whereas WT and p.A159T prohormones and/or processed products were located in the tips of cellular processes. Reduced levels of AVP in supernatant culture medium of p.G96D and p.C98G transfected cells in comparison to p.A159T and WT cells were found.
  
  
  CONCLUSIONS
  We conclude that the p.G96D and p.C98G mutations cause adFNDI in the two reported families. The sequence variant p.A159T does not seem to have disease-causing effects.
authors.affiliation: Children's Hospital, Technical University Dresden, Dresden, Germany.
authors.forename: C M
authors.initials: CM
authors.lastname: Hedrich
authors.forename: A
authors.initials: A
authors.lastname: Zachurzok-Buczynska
authors.forename: A
authors.initials: A
authors.lastname: Gawlik
authors.forename: S
authors.initials: S
authors.lastname: Russ
authors.forename: G
authors.initials: G
authors.lastname: Hahn
authors.forename: K
authors.initials: K
authors.lastname: Koehler
authors.forename: E
authors.initials: E
authors.lastname: Malecka-Tendera
authors.forename: A
authors.initials: A
authors.lastname: Huebner
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D020790:Diabetes Insipidus, Neurogenic / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D030342:Genetic Diseases, Inborn / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D020125:Mutation, Missense; D009481:Neurophysins / Q000235:genetics* / Q000378:metabolism*; D010375:Pedigree; D011044:Poland
chemical_list: D009481:Neurophysins