Autosomal recessive familial neurohypophyseal diabetes insipidus with continued secretion of mutant weakly active vasopressin

Michael D. Willcutts, Eric Felner, Perrin C. White

Research output: Contribution to journalArticle

67 Citations (Scopus)

Abstract

Familial neurohypophyseal diabetes insipidus is an autosomal dominant disorder characterized by post natal development of arginine vasopressin (AVP) deficiency due to mutations in the AVP gene. All published mutations affect the signal peptide or the neurophysin-II carrier protein and are presumed to interfere with processing of the preprohormone, leading to neuronal damage. We studied an unusual Palestinian family consisting of asymptomatic first cousin parents and three children affected with neurohypophyseal diabetes insipidus, suggesting autosomal recessive inheritance. All three affected children were homozygous and the parents heterozygous for a single novel mutation (C301→T) in exon 1, replacing Pro7 of mature AVP with Leu (Leu-AVP). Leu-AVP was a weak agonist with ~ 30-fold reduced binding to the human V2 receptor. Measured by radioimmunoassay with a synthetic Leu-AVP standard, serum Leu-AVP levels were elevated in all three children and further increased during water deprivation to as high as 30 times normal. The youngest child (2 years old) was only mildly affected but had Leu-AVP levels similar to her severely affected 8-year-old brother, suggesting that unknown mechanisms may partially compensate for a deficiency of active AVP in very young children.

Original languageEnglish (US)
Pages (from-to)1303-1307
Number of pages5
JournalHuman Molecular Genetics
Volume8
Issue number7
DOIs
StatePublished - 1999

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Neurogenic Diabetes Insipidus
Arginine Vasopressin
Vasopressins
Mutation
Parents
Neurophysins
Water Deprivation
Vasopressin Receptors
Protein Sorting Signals
Radioimmunoassay
Siblings
Exons
Carrier Proteins

ASJC Scopus subject areas

  • Genetics

Cite this

Autosomal recessive familial neurohypophyseal diabetes insipidus with continued secretion of mutant weakly active vasopressin. / Willcutts, Michael D.; Felner, Eric; White, Perrin C.

In: Human Molecular Genetics, Vol. 8, No. 7, 1999, p. 1303-1307.

Research output: Contribution to journalArticle

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