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Autosomal Dominant Neurohypophyseal Diabetes Insipidus Associated with a Missense Mutation Encoding Gly²³Val in Neurophysin II¹

Division of Endocrinology, Children’s Hospital Medical Center (P.C.G., D.R.R.), Cincinnati, Ohio 45229; and Dipartimento di Scienze Ginecologiche, Ostetriche e Pediatriche, Universita Degli Studi di Modena (S.B.), 41100 Modena, Italy

Address all correspondence and requests for reprints to: David Repaske, Ph.D., M.D., NWM-1 TCHRF, Children’s Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, Ohio 45229-3039. E-mail: repaskdr{at}ucunix.san.uc.edu

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 (G¹⁷⁵⁸T) encoding the amino acid substitution Gly²³Val 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.

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