title: Identification of a novel mutation in the arginine vasopressin-neurophysin II gene affecting the sixth intrachain disulfide bridge of the neurophysin II moiety.
abstract: OBJECTIVE
  Most mutations of the arginine vasopressin-neurophysin II (AVP-NPII) gene cause autosomal dominant familial neurohypophyseal diabetes insipidus (adFNDI). Such mutations are predicted to alter the three-dimensional structure of the prohormone, which accumulates in the cell body, ultimately leading to neuronal degeneration and hormonal deficit. In this study we describe the case of a 26-year-old female reporting a long-lasting history of polyuria/polydipsia. The father of the patient was affected by diabetes insipidus and was under desmopressin treatment until the time of his death. Nevertheless, the patient had never been subjected to endocrine evaluation.
  
  
  METHODS
  Clinical and genetic studies were performed. An 8-h fluid deprivation test plus desmopressin challenge and a 5% saline solution test were performed, in order to confirm the diagnosis. DNA was extracted from peripheral blood lymphocytes and subjected to direct sequencing of the entire coding region of the AVP-NPII gene.
  
  
  CONCLUSIONS
  Clinical assessment of the patient confirmed the diagnosis of neurohypophyseal diabetes insipidus. Desmopressin treatment was started, which effectively reversed the polyuria/ polydipsia syndrome. Genetic analysis revealed a novel mutation (1665T>A) in exon 2 of the AVP-NPII gene, disrupting one of the disulfide bonds present in the NPII moiety which play a fundamental role in determining the proper folding of the molecule. In summary, in the present study we have described a novel mutation of the AVP-NPII gene, which is consistent with the malfolding/toxicity hypothesis underlying the pathogenesis of adFNDI.
authors.affiliation: Medical Genetics, Department of Clinical Physiopathology, University of Florence, 50139 Florence, Italy.
authors.forename: Silvana
authors.initials: S
authors.lastname: Baglioni
authors.forename: Giovanni
authors.initials: G
authors.lastname: Corona
authors.forename: Mario
authors.initials: M
authors.lastname: Maggi
authors.forename: Mario
authors.initials: M
authors.lastname: Serio
authors.forename: Alessandro
authors.initials: A
authors.lastname: Peri
mesh_terms: D000328:Adult; D001127:Arginine Vasopressin / Q000235:genetics*; D001483:Base Sequence; D003894:Deamino Arginine Vasopressin / Q000627:therapeutic use; D020790:Diabetes Insipidus, Neurogenic / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics* / Q000523:psychology; D004327:Drinking Behavior / Q000187:drug effects; D005260:Female; D006801:Humans; D015394:Molecular Structure; D009154:Mutation; D009481:Neurophysins / Q000737:chemistry* / Q000235:genetics*; D010121:Oxytocin / Q000235:genetics*; D010375:Pedigree; D011141:Polyuria / Q000209:etiology; D011498:Protein Precursors / Q000235:genetics*; D012076:Renal Agents / Q000627:therapeutic use
chemical_list: D009481:Neurophysins; D011498:Protein Precursors; D012076:Renal Agents; D001127:Arginine Vasopressin; D010121:Oxytocin; D003894:Deamino Arginine Vasopressin