A missense mutation in the arginine-vasopressin neurophysin-II gene causes autosomal dominant neurohypophyseal diabetes insipidus in a Chinese family.

Abstract

BACKGROUND:

Familial neurohypophyseal diabetes insipidus, an autosomal dominant disorder, is mostly caused by mutations in the genes that encode AVP or its intracellular binding protein, neurophysin-II. The mutations lead to aberrant preprohormone processing and progressive destruction of AVP-secreting cells, which gradually manifests a progressive polyuria and polydipsia during early childhood, and a disorder of water homeostasis.

OBJECTIVE:

We characterized the clinical and biochemical features, and sequenced the AVP neurophysin-II(AVP-NPII) gene of the affected individuals with autosomal dominant neurohypophyseal diabetes insipidus(ADNDI)to determine whether this disease was genetically determined.

PATIENTS AND METHODS:

We obtained the histories of eight affected and four unaffected family individuals. The diagnosis of ADNDI was established using a water deprivation test and exogenous AVP administration. For molecular analysis, genomic DNA was extracted and the AVP-NPII gene was amplified using polymerase chain reaction and sequenced.

RESULTS:

The eight affected individuals showed different spectra of age of onsets (7-15 years) and urine volumes (132-253 ml/kg/24 h). All affected individuals responded to vasopressin administration, with a resolution of symptoms and an increase in urine osmolality by more than 50%. The characteristic hyperintense signal in the posterior pituitary on T1-weighted magnetic resonance imaging was absent in six family members and present in one. Sequencing analysis revealed a missense heterozygous mutation 1516G > T (Gly17Val) in exon 2 of the AVP-NPII gene among the ADNDI individuals.

CONCLUSIONS:

We identified a missense mutation in the AVP-NPII gene and the same mutation showed different spectra of age of onsets and urine volumes in a new Chinese family with ADNDI. The mutation may provide a molecular basis for understanding the characteristics of NPII and add to our knowledge of the pathogenesis of ADNDI, which would allow the presymptomatic diagnosis of asymptomatic subjects.

• Authors: Dan Ye, FengQin Dong, WeiQin Lu, Zhe Zhang, XunLiang Lu, ChengJiang Li, YanNing Liu
• Journal: Clinical endocrinology (Clin Endocrinol (Oxf)) Vol. 78 Issue 6 Pg. 920-5 (Jun 2013) ISSN: 1365-2265 [Electronic] England
• PMID: 23252994 (Publication Type: Journal Article)
• Copyright: © 2012 John Wiley & Sons Ltd.

Chemical References

• Neurophysins
• Saline Solution, Hypertonic
• Arginine Vasopressin

Topics

• Adolescent
• Age of Onset
• Arginine Vasopressin (genetics, metabolism)
• Asian People (genetics)
• Child
• Diabetes Insipidus, Neurogenic (genetics)
• Female
• Humans
• Kidney Concentrating Ability
• Male
• Middle Aged
• Mutation, Missense
• Neurophysins (genetics)
• Osmolar Concentration
• Pedigree
• Saline Solution, Hypertonic
• Water Deprivation