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-neurophysin 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 encoding neurophysin II in the index patient. This amino acid change is thought to result in the formation of an incorrectly folded hormone precursor, which may lead to chronic neurotoxicity and explain the dominant inheritance of the disease.
D001127:Arginine Vasopressin / Q000235:genetics*; D004252:DNA Mutational Analysis; D003919:Diabetes Insipidus / Q000235:genetics*; D005260:Female; D005799:Genes, Dominant; D006801:Humans; D008297:Male; D008957:Models, Genetic; D009154:Mutation; D009481:Neurophysins / Q000235:genetics*; D010121:Oxytocin; D010375:Pedigree; D011498:Protein Precursors / Q000235:genetics*