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A novel variation in the AVP gene resulting in familial neurohypophyseal diabetes insipidus in a large Italian kindred

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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 7-year follow-up MRI scan in one subject. DNA sequence analysis revealed heterozygousity for a novel g.1785T > C gene variation predicting a p.Leu63Pro 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 unaffected.

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Acknowledgments

We 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.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Pediatrics, Aarhus University Hospital, Brendstrupgaardsvej 100, 8200, Aarhus, Denmark

    Camilla Birkegaard, Jane H. Christensen & Søren Rittig

  2. Department of Biomedicine, Aarhus University, Aarhus, Denmark

    Jane H. Christensen

  3. Department of Internal Medicine, University of Perugia, Perugia, Italy

    Alberto Falorni, Stefania Marzotti & Viviana Minarelli

  4. Research Unit for Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark

    Niels Gregersen

Authors
  1. Camilla Birkegaard
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  2. Jane H. Christensen
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  3. Alberto Falorni
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  4. Stefania Marzotti
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  5. Viviana Minarelli
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  6. Niels Gregersen
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  7. Søren Rittig
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Correspondence to Camilla Birkegaard.

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Birkegaard, C., Christensen, J.H., Falorni, A. et al. A novel variation in the AVP gene resulting in familial neurohypophyseal diabetes insipidus in a large Italian kindred. Pituitary 16, 152–157 (2013). https://doi.org/10.1007/s11102-012-0392-x

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  • DOI: https://doi.org/10.1007/s11102-012-0392-x

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