ClinVar

In a Dutch family in which familial neurohypophyseal diabetes insipidus (125700) had been diagnosed, Abbes et al. (2000) identified a cysteine (TGC)-to-glycine (GGC) substitution at codon 116 of the AVP gene. Nijenhuis et al. (2001) analyzed the intracellular transport of the mutant vasopressin prohormone in stably transfected cell lines that contained a regulated secretory pathway. Nijenhuis et al. (2001) referred to the mutation as NP85C-G. In 2 children from this kindred they found that growth retardation was an important early sign that responded to substitution therapy with 1-desamino-8-D-arginine vasopressin. To obtain clues about the basis for the dominant inheritance of familial neurohypophyseal diabetes insipidus, they analyzed the trafficking and processing of the mutant vasopressin prohormone in cell lines by metabolic labeling and immunoprecipitation. The mutant vasopressin prohormone was retained in the endoplasmic reticulum and thus was not processed to vasopressin. The defect was not caused by dimerization of the vasopressin prohormone via its unpaired cysteine residue. High-level expression of the mutant vasopressin prohormone in cell lines resulted in strong accumulation in the endoplasmic reticulum and an altered morphology of this organelle. The authors hypothesized that disturbance of the endoplasmic reticulum results in dysfunction and ultimately cell death of the cells expressing the mutant prohormone.