Authors: Camilla Birkegaard Jane H Christensen Alberto Falorni Stefania Marzotti Viviana Minarelli Niels Gregersen Søren Rittig
Publish Date: 2012/06/14
Volume: 16, Issue: 2, Pages: 152-157
Abstract
Familial neurohypophyseal diabetes insipidus FNDI is mostly an autosomal dominant inherited disorder presenting with severe polydipsia and polyuria typically in early childhood To date 69 different variations in the AVP gene encoding the AVP prohormone have been identified in autosomal dominant FNDI adFNDI In this study we present a family of seven generations in which a novel variation in the AVP gene seems to cause adFNDI Clinical assessment by 24 h urine collection water deprivation test desmopressin dDAVP challenge and magnetic resonance imaging MRI of the posterior pituitary are presented The diagnosis of adFNDI was confirmed by direct DNA sequence analysis of the AVP gene Inheritance pattern and clinical history clearly pointed towards adFNDI Inability of concentrating urine upon dehydration was demonstrated by a water deprivation test and neurohypophyseal diabetes insipidus was strongly suspected after dDAVP administration during which renal concentration ability quadrupled MRI revealed a very weak pituitary “bright spot” in each of six subjects and a further reduction in the size of the neurohypophysis in a 7year followup MRI scan in one subject DNA sequence analysis revealed heterozygousity for a novel g1785T C gene variation predicting a pLeu63Pro substitution in four affected subjects Genetic testing in the diagnostic evaluation of families in which diabetes insipidus segregates is highly recommended in that interpretation of clinical assessments can be difficult Furthermore presymptomatic diagnosis can ease the parental concern of the carrier status of their offspring and also avoid unnecessary surveillance of those being unaffectedWe are indebted to the members of the family for their participation We thank Jane H Knudsen and Margrethe Kjeldsen for their skilled laboratory assistance This work was supported by the Novo Nordisk Foundation and the Health Research Fund of Central Denmark Region
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