AVP – Neurohypophyseal Diabetes Insipidus

Familial central diabetes insipidus is an inherited disorder characterized by autosomal dominant arginine vasopressin deficiency. Mutations in the arginine vasopressin-neurophysin II (AVP-NPII) precursor cause inadequate hormone synthesis and secretion, leading to the clinical triad of polyuria, polydipsia, and hypernatremia. Two Caucasian kindreds were studied, revealing a heterozygous missense substitution p.Cys61Ser and a novel heterozygous nonsense change p.Gln83Ter in AVP-NPII (both variants segregated with disease and were absent in controls) (PMID:12012274). Both variants map to the neurophysin II coding region of exon 2 and exon 3, respectively, predicting destabilization of the AVP precursor and premature chain termination. These findings support a haploinsufficiency mechanism, in which loss of one functional allele reduces circulating vasopressin below the threshold required for water homeostasis.

No additional functional assays of AVP-NPII variants have been reported to date, though the truncating allele is predicted to undergo nonsense-mediated decay and the missense allele to interfere with proper folding of the AVP precursor. No conflicting or refuting evidence has been described. Genetic testing for AVP exonic variants provides a reliable molecular diagnostic for familial neurohypophyseal diabetes insipidus. Early identification of pathogenic AVP variants enables anticipatory management of fluid balance and tailored desmopressin therapy.

References

• Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association • 2002 • Identification of a novel mutation in the arginine vasopressin-neurophysin II gene in familial central diabetes insipidus. PMID:12012274

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