A novel mutation (R97C) in the neurophysin moiety of prepro-vasopressin-neurophysin II associated with autosomal-dominant neurohypophyseal diabetes insipidus

Autosomal-dominant familial neurohypophyseal diabetes insipidus (adFNDI) is caused by heterozygous mutations in the gene encoding vasopressin-neurophy sin II (AVP-NPII) on chromosome 20p13. We analyzed the AVP-NP II gene in a family with adFNDI by direct sequencing. A novel C to T transition (289C--> T in the cDNA, resulting in the substitution of Arg 97 by Cys (R97C) in the prepro-AVP-NPII precursor molecule) was identified in the gene region enco ding neurophysin II in the index patient. This amino acid change is thought to result in the formation of an incorrectly folded hormone precursor, whi ch may lead to chronic neurotoxicity and explain the dominant inheritance o f the disease. (C) 1999 Academic Press.