Autosomal dominant neurohypophyseal diabetes insipidus associated with a missense mutation encoding Gly23-->Val in neurophysin II.
Autosomal dominant neurohypophyseal diabetes insipidus (ADNDI) is an inherited disease caused by progressive degeneration of the magnocellular neurons of the hypothalamus leading to decreased ability to produce the hormone arginine vasopressin (AVP). Affected individuals are not symptomatic at birth, but usually develop diabetes insipidus at 1-6 yr of age. 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. An affected girl who presented at 9 months of age and her similarly affected younger brother and father were all found to have a novel missense mutation (G1758-->T) encoding the amino acid substitution Gly23-->Val within NPII. The mutation was confirmed by restriction endonuclease analysis. A T1-weighted magnetic resonance imaging of the father's pituitary gland demonstrates an attenuated posterior pituitary bright spot. This mutation may be valuable for developing models of dominantly inherited neurodegeneration, as the early age of onset of symptoms suggests that this mutation may be particularly deleterious to the magnocellular neuron.
Gagliardi
P C
PC
Division of Endocrinology, Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA.
Bernasconi
S
S
Repaske
D R
DR
D001127:Arginine Vasopressin / Q000235:genetics*; D004247:DNA / Q000737:chemistry; D003919:Diabetes Insipidus / Q000235:genetics* / Q000503:physiopathology; D005091:Exons; D005260:Female; D005998:Glycine / Q000235:genetics*; D006801:Humans; D007027:Hypothalamic Diseases / Q000235:genetics; D007223:Infant; D008279:Magnetic Resonance Imaging; D008297:Male; D009154:Mutation; D009481:Neurophysins / Q000235:genetics*; D010375:Pedigree; D010904:Pituitary Gland, Posterior / Q000473:pathology / Q000503:physiopathology*; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D014633:Valine / Q000235:genetics*
D009481:Neurophysins; D001127:Arginine Vasopressin; D004247:DNA; D014633:Valine; D005998:Glycine