title: A missense mutation in the arginine-vasopressin neurophysin-II gene causes autosomal dominant neurohypophyseal diabetes insipidus in a Chinese family.
abstract: BACKGROUND
  Familial neurohypophyseal diabetes insipidus, an autosomal dominant disorder, is mostly caused by mutations in the genes that encode AVP or its intracellular binding protein, neurophysin-II. The mutations lead to aberrant preprohormone processing and progressive destruction of AVP-secreting cells, which gradually manifests a progressive polyuria and polydipsia during early childhood, and a disorder of water homeostasis.
  
  
  OBJECTIVE
  We characterized the clinical and biochemical features, and sequenced the AVP neurophysin-II(AVP-NPII) gene of the affected individuals with autosomal dominant neurohypophyseal diabetes insipidus(ADNDI)to determine whether this disease was genetically determined.
  
  
  METHODS
  We obtained the histories of eight affected and four unaffected family individuals. The diagnosis of ADNDI was established using a water deprivation test and exogenous AVP administration. For molecular analysis, genomic DNA was extracted and the AVP-NPII gene was amplified using polymerase chain reaction and sequenced.
  
  
  RESULTS
  The eight affected individuals showed different spectra of age of onsets (7-15 years) and urine volumes (132-253 ml/kg/24 h). All affected individuals responded to vasopressin administration, with a resolution of symptoms and an increase in urine osmolality by more than 50%. The characteristic hyperintense signal in the posterior pituitary on T1-weighted magnetic resonance imaging was absent in six family members and present in one. Sequencing analysis revealed a missense heterozygous mutation 1516G > T (Gly17Val) in exon 2 of the AVP-NPII gene among the ADNDI individuals.
  
  
  CONCLUSIONS
  We identified a missense mutation in the AVP-NPII gene and the same mutation showed different spectra of age of onsets and urine volumes in a new Chinese family with ADNDI. The mutation may provide a molecular basis for understanding the characteristics of NPII and add to our knowledge of the pathogenesis of ADNDI, which would allow the presymptomatic diagnosis of asymptomatic subjects.
authors.affiliation: Department of Endocrinology and Metabolism, The First Affiliated Hospital of Medical School of Zhejiang University, Zhejiang, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Ye
authors.forename: FengQin
authors.initials: F
authors.lastname: Dong
authors.forename: WeiQin
authors.initials: W
authors.lastname: Lu
authors.forename: Zhe
authors.initials: Z
authors.lastname: Zhang
authors.forename: XunLiang
authors.initials: X
authors.lastname: Lu
authors.forename: ChengJiang
authors.initials: C
authors.lastname: Li
authors.forename: YanNing
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000293:Adolescent; D017668:Age of Onset; D001127:Arginine Vasopressin / Q000235:genetics* / Q000378:metabolism*; D044466:Asian People / Q000235:genetics; D002648:Child; D020790:Diabetes Insipidus, Neurogenic / Q000235:genetics*; D005260:Female; D006801:Humans; D007671:Kidney Concentrating Ability; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D009481:Neurophysins / Q000235:genetics*; D009994:Osmolar Concentration; D010375:Pedigree; D012462:Saline Solution, Hypertonic; D014868:Water Deprivation
chemical_list: D009481:Neurophysins; D012462:Saline Solution, Hypertonic; D001127:Arginine Vasopressin