A new missense mutation of the vasopressin-neurophysin II gene in a family with neurohypophyseal diabetes insipidus

Horm Res. 2003;60(3):143-7. doi: 10.1159/000072526.

Abstract

Objective: Autosomal dominant familial neurohypophyseal diabetes insipidus is a rare disorder characterized by polydipsia and polyuria. We present the results of the molecular analysis of the AVP-NPII gene of a German kindred.

Methods: All three exons of the gene were amplified by polymerase chain reaction and sequenced.

Results: In 7 affected individuals a new missense mutation (1770G > T) in exon 2 was found predicting a cysteine to phenylalanine substitution at codon 58 in the neurophysin II domain (NPII).

Conclusion: As a result of this mutation a cysteine residue is exchanged, which is involved in a disulfide bond with cysteine 44 of the NPII moiety, hypothesizing that the resulting misfolded protein may lead to chronic neurotoxicity by accumulation of these products in the endoplasmatic reticulum.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Arginine Vasopressin / genetics*
  • Base Sequence
  • Child
  • Diabetes Insipidus, Neurogenic / genetics*
  • Female
  • Genetic Carrier Screening
  • Heterozygote
  • Humans
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Mutation, Missense
  • Neurophysins / genetics*
  • Pedigree

Substances

  • Neurophysins
  • Arginine Vasopressin