ClinVar

In a consanguineous Palestinian family with neurohypophyseal diabetes insipidus (125700), Willcutts et al. (1999) identified a C-to-T transition at nucleotide 301 (C301T) in exon 1 of the AVP gene, replacing proline-7 of mature AVP with leucine (Leu-AVP). All 3 affected children were homozygous for the mutation, and the parents were heterozygous. The authors determined that Leu-AVP is a weak agonist with approximately 30-fold reduced binding to the human V2 receptor. Serum Leu-AVP levels were elevated in all 3 children and further increased during water deprivation to as high as 30 times normal, as measured by radioimmunoassay. The youngest child (2 years old) was only mildly affected, but had Leu-AVP levels similar to her severely affected 8-year-old brother, suggesting to the authors that unknown mechanisms may partially compensate for a deficiency of active AVP in very young children.

Christensen et al. (2004) investigated the cellular handling of the P26L prohormone (P7L in the mature AVP protein) by heterologous expression in neurogenic and neuronal cell lines. Secretion of P26L prohormone was unaffected compared to wildtype prohormone. Confocal laser scanning microscopy showed localization of the P26L prohormone and/or processed products in secretory granules in the cellular processes. Christensen et al. (2004) concluded that the recessive P26L mutation does not seem to affect intracellular trafficking but rather the final processing of the AVP prohormone.