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A novel AVP gene mutation in a Turkish family with neurohypophyseal diabetes insipidus

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Abstract

Purpose

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.

Conclusion

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.

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Acknowledgments

The manuscript was edited for proper English language by a highly qualified native English speaking editor in Bezmialem Vakif University Professional English for Medical Purpose (BVUPSO-101-03/15).

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Authors and Affiliations

  1. Department of Endocrinology and Metabolism, Bezmialem University, Vatan Caddesi, 34093, Istanbul, Turkey

    M. Ilhan, O. Karaman & E. Tasan

  2. Department of Molecular Biology and Genetics, Halic University, Istanbul, Turkey

    N. O. Tiryakioglu

  3. Division of Medical Genetics, Department of Internal Medicine, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey

    E. Coskunpinar

  4. Department of Internal Medicine, Bezmialem University, Vatan Caddesi, 34093, Istanbul, Turkey

    R. S. Yildiz & S. Turgut

  5. Department of Basic Oncology, Oncology Institute, Istanbul University, Istanbul, Turkey

    D. Tiryakioglu

  6. Department of Radiology, Bezmialem University, Vatan Caddesi, 34093, Istanbul, Turkey

    H. Toprak

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  1. M. Ilhan
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Correspondence to M. Ilhan.

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This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.

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The study was conducted in compliance with the Declaration of Helsinki.

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Informed consent was obtained from all individual participants included in the study.

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Ilhan, M., Tiryakioglu, N.O., Karaman, O. et al. A novel AVP gene mutation in a Turkish family with neurohypophyseal diabetes insipidus. J Endocrinol Invest 39, 285–290 (2016). https://doi.org/10.1007/s40618-015-0357-9

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  • DOI: https://doi.org/10.1007/s40618-015-0357-9

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