Six novel mutations in the arginine vasopressin gene in 15 kindreds with autosomal dominant familial neurohypophyseal diabetes insipidus give further insight into the pathogenesis.
The molecular basis of autosomal dominant neurohypophyseal diabetes insipidus, a hereditary deficiency of vasopressin, was determined by nucleotide sequence analysis of the arginine vasopressin-neurophysin-II gene.
We examined plasma arginine-vasopressin concentrations by radioimmunoassay in two brothers, aged 6 and 7.5 years, with familial central diabetes insipidus inherited as an autosomal dominant trait.
We investigated two Caucasian families with a typical autosomal dominant trait of familial central diabetes insipidus, defined by deficiency of arginine vasopressin.
We previously reported three distinct mutations in the AVP gene in Japanese familial central diabetes insipidus pedigrees that result in a substitution of Ser for Gly57 in the neurophysin-II (NPII) moiety of the AVP precursor, a substitution of Thr for Ala at the COOH-terminus of the signal peptide, and a deletion of Glu47 in the NPII moiety.
We suggest that AVP would undergo accelerated proteolytic degradation, and this mechanism would be involved in the pathogenesis of DI in this pedigree.