DETECTION OF A NOVEL ARGININE-VASOPRESSIN DEFECT BY DIDEOXY FINGERPRINTING

Autosomal dominant neurohypophyseal diabetes insipidus is a familial f orm of diabetes insipidus. This disorder is associated with variable l evels of arginine vasopressin (AVP) and diabetes insipidus of varying severity, which responds to exogenous AVP. To determine the molecular basis of autosomal dominant neurohypophyseal diabetes insipidus, the A VP genes of members of a large kindred were analyzed. A new method, ca lled dideoxy fingerprinting, was used to detect an AVP mutation that w as characterized by DNA sequencing. The novel defect found changes the last codon of the AVP signal peptide from alanine to threonine, which should perturb cleavage of mature AVP from its precursor protein and inhibit its secretion or action.