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Ze’ev Hochberg, Anita van Lieburg, Lea Even, Benjamin Brenner, Naomi Lanir, Bernard A. van Oost, Nine V.A.M. Knoers, Autosomal Recessive Nephrogenic Diabetes Insipidus Caused by an Aquaporin-2 Mutation*, The Journal of Clinical Endocrinology & Metabolism, Volume 82, Issue 2, 1 February 1997, Pages 686–689, https://doi.org/10.1210/jcem.82.2.3781
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Abstract
Vasopressin V2 receptors, expressed from an x-chromosomal gene, are involved in antidiuresis, but also in release of coagulation factor VIII and von Willebrand factor (vWF). The present study describes autosomal recessive nephrogenic diabetes insipidus (NDI) in a large cluster of patients in Israel’s Lower-Galilee. Evidence for an intact V2 receptor was concluded by their normal increase in factor VIII and vWF after desmopressin infusion. Thus, in these patients a defect in the pathway beyond the V2 receptor was suspected. The recent cloning of the human Aquaporin-2 gene enabled us to test this gene as a candidate for such a postreceptor defect. Direct sequencing of the Aquaporin-2 gene revealed a G298T substitution causing a Gly100Stop nonsense mutation in the third transmembrane region. Because this putative disease-causing mutation was identified in index patients of different families, we suggest that all patients are descendants of a common ancestor. Thus, this new entity is characterized by an autosomal recessive NDI. The differential response of clotting factors and urine osmolality to desmopressin may provide a simple tool for clinical diagnosis of a V2-postreceptor defect. The early stop-codon of Aquaporin-2 results in complete resistance to vasopressin antidiuretic effect.
