title: A novel AVP gene mutation in a Turkish family with neurohypophyseal diabetes insipidus.
abstract: OBJECTIVE
  Familial neurohypophyseal diabetes insipidus (FNDI) is a rare, autosomal dominant, inherited disorder which is characterized by severe polydipsia and polyuria generally presenting in early childhood. In the present study, we aimed to analyze the AVP gene in a Turkish family with FNDI.
  
  
  METHODS
  Four patients with neurohypophyseal diabetes insipidus and ten healthy members of the family were studied. Diabetes insipidus was diagnosed by the water deprivation test in affected family members. Mutation analysis was performed by sequencing the whole coding region of AVP-NPII gene using DNA isolated from peripheral blood samples.
  
  
  RESULTS
  Urine osmolality was low (<300 mOsm/kg) during water deprivation test, and an increase more than 50 % in urine osmolality and recovery of the symptoms were observed by the administration of desmopressin in all patients. Plasma copeptin levels were lower than expected according to plasma osmolality. Pituitary MRI revealed partial empty sella with a bright spot in index patient and a normal neurohypophysis in the other affected subjects. Genetic screening revealed a novel, heterozygous mutation designated as c.-3A>C in all patients.
  
  
  CONCLUSIONS
  c.-3A>C mutation in 5'UTR of AVP gene in this family might lead to the truncation of signal peptide, aggregation of AVP in the cytoplasm instead of targeting in the endoplasmic reticulum, thereby could disrupt AVP secretion without causing neuronal cytotoxicity, which might explain the presence of bright spot. The predicted effect of this mutation should be investigated by further in vitro molecular studies.
authors.affiliation: Department of Endocrinology and Metabolism, Bezmialem University, Vatan Caddesi, 34093, Istanbul, Turkey. muzoilhan@yahoo.com.
authors.forename: M
authors.initials: M
authors.lastname: Ilhan
authors.affiliation: Department of Molecular Biology and Genetics, Halic University, Istanbul, Turkey.
authors.forename: N O
authors.initials: NO
authors.lastname: Tiryakioglu
authors.affiliation: Department of Endocrinology and Metabolism, Bezmialem University, Vatan Caddesi, 34093, Istanbul, Turkey.
authors.forename: O
authors.initials: O
authors.lastname: Karaman
authors.affiliation: Division of Medical Genetics, Department of Internal Medicine, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey.
authors.forename: E
authors.initials: E
authors.lastname: Coskunpinar
authors.affiliation: Department of Internal Medicine, Bezmialem University, Vatan Caddesi, 34093, Istanbul, Turkey.
authors.forename: R S
authors.initials: RS
authors.lastname: Yildiz
authors.affiliation: Department of Internal Medicine, Bezmialem University, Vatan Caddesi, 34093, Istanbul, Turkey.
authors.forename: S
authors.initials: S
authors.lastname: Turgut
authors.affiliation: Department of Basic Oncology, Oncology Institute, Istanbul University, Istanbul, Turkey.
authors.forename: D
authors.initials: D
authors.lastname: Tiryakioglu
authors.affiliation: Department of Radiology, Bezmialem University, Vatan Caddesi, 34093, Istanbul, Turkey.
authors.forename: H
authors.initials: H
authors.lastname: Toprak
authors.affiliation: Department of Endocrinology and Metabolism, Bezmialem University, Vatan Caddesi, 34093, Istanbul, Turkey.
authors.forename: E
authors.initials: E
authors.lastname: Tasan
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D020790:Diabetes Insipidus, Neurogenic / Q000175:diagnosis / Q000235:genetics*; D005190:Family; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009481:Neurophysins / Q000235:genetics*; D010375:Pedigree; D011379:Prognosis; D011498:Protein Precursors / Q000235:genetics*; D014421:Turkey; D014667:Vasopressins / Q000235:genetics*; D055815:Young Adult
chemical_list: C438657:AVP protein, human; D009481:Neurophysins; D011498:Protein Precursors; D014667:Vasopressins
keywords: Diabetes insipidus; Familial; Inherited; Mutation