HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

A novel deletion partly removing the AVP gene causes autosomal recessive inheritance of early-onset neurohypophyseal diabetes insipidus.

Abstract
Familial neurohypophyseal diabetes insipidus (FNDI) typically presents with age-dependent penetrance and autosomal dominant inheritance caused by missense variations in one allele of the AVP gene encoding the arginine vasopressin (AVP) prohormone. We present the molecular genetic characteristics underlying an unusual form of FNDI occurring with very early onset and seemingly autosomal recessive inheritance. By DNA amplification and sequencing, we identified a novel variant allele of the AVP gene carrying a 10,396 base pair deletion involving the majority of the AVP gene as well as its regulatory sequences in the intergenic region between the AVP and the OXT gene, encoding the oxytocin prohormone. We found two chromosomes carrying the deletion in affected family members and one in unaffected family members suspected to transmit the deleted allele. Whole-genome array analysis confirmed the results and excluded the presence of any additional major pathogenic abnormalities. The deletion is predicted to abolish the transcription of the AVP gene, thus the fact that family members heterozygous for the deletion remain healthy argues, in general, against haploinsufficiency as the pathogenic mechanism FNDI. Accordingly, our data is strong support to the prevailing idea that dominant inheritance of FNDI is due to a dominant-negative effect exerted by variant AVP prohormone.
AuthorsJ H Christensen, H Kvistgaard, J Knudsen, G Shaikh, J Tolmie, S Cooke, S Pedersen, T J Corydon, N Gregersen, S Rittig
JournalClinical genetics (Clin Genet) Vol. 83 Issue 1 Pg. 44-52 (Jan 2013) ISSN: 1399-0004 [Electronic] Denmark
PMID22168581 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright© 2011 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.
Chemical References
  • AVP protein, human
  • Neurophysins
  • Protein Precursors
  • Vasopressins
Topics
  • Age of Onset
  • Alleles
  • Diabetes Insipidus, Neurogenic (genetics, physiopathology)
  • Female
  • Genes, Recessive
  • Heterozygote
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Mutation
  • Neurophysins (genetics)
  • Pedigree
  • Pregnancy
  • Protein Precursors (genetics)
  • Sequence Deletion (genetics)
  • Vasopressins (genetics)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: