Autosomal dominant neurohypophyseal diabetes insipidus (adNDI) is caused by arginine vasopressin (AVP) deficiency resulting from mutations in the AVP-NPII gene encoding the AVP preprohormone.
This finding of a novel mutation substituting cysteine with phenylalanine in one AVP-NPII gene allele supports the hypothesis that inability to form normal disulfide bonds in neurophysin II leads to ADNDI.
Antidiuretic function, magnetic resonance imaging (MRI) of the posterior pituitary and AVP-NPII gene analysis were performed in 10 affected members of three unreported families with adFNDI.
These results suggest that adNDI is a progressive disease associated with chronic loss of the magnocellular neurons that supply AVP to the posterior pituitary but preservation of the parvocellular neurons that supply AVP and CRH to the median eminence and stimulate ACTH production during hypernatremia.
We conclude that (1) a novel G1773A transition in exon 2 of the AVP-NPII gene causes ADNDI in the large Cypriot kindred studied, (2) this mutation is predicted to encode a CYS59TYR substitution in NPII, and (3) MRI studies of the posterior pituitary lobes of affected family members show either a decreased intensity or a complete absence of the bright spot in all cases studied.
We evaluated the AVP-NPII genes in two independent families with ADNDI and identified a mutation (C280-->T) in the coding sequence for the signal peptide of the prepro-AVP-NPII precursor in both families.
The genetic locus of the disease is the AVP-neurophysin II (NPII) gene, and mutations that cause ADNDI have been found in both the signal peptide of the prepro-AVP-NPII precursor and within NPII itself.
Magnetic resonance imaging of posterior pituitary for evaluation of the neurohypophyseal function in idiopathic and autosomal dominant neurohypophyseal diabetes insipidus.
In this family, the autosomal dominant neurohypophyseal diabetes insipidus phenotype cosegregates with a point mutation in a region of the AVP-neurophysin-II gene which codes for the carboxy-terminal domain of neurophysin-II.
We examined the nucleotide sequence of the arginine vasopressin-neurophysin II gene in three kindreds with autosomal dominant neurohypophyseal diabetes insipidus.
Cloning and nucleotide sequence analysis of both alleles of the AVP-NP gene present in a Dutch ADNDI family reveals a point mutation in one allele of the affected family members.
The status of the arginine vasopressin-neurophysin-II (AVP-NPII) gene was studied in three families with autosomal dominant neurohypophyseal diabetes insipidus (AD-NDI).