PMID- 10369876
OWN - NLM
STAT- MEDLINE
DCOM- 19990816
LR  - 20190513
IS  - 0964-6906 (Print)
IS  - 0964-6906 (Linking)
VI  - 8
IP  - 7
DP  - 1999 Jul
TI  - Autosomal recessive familial neurohypophyseal diabetes insipidus with continued
      secretion of mutant weakly active vasopressin.
PG  - 1303-7
AB  - 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 
      approximately 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.
FAU - Willcutts, M D
AU  - Willcutts MD
AD  - Division of Pediatric Endocrinology, University of Texas Southwestern Medical
      Center, 5323 Harry Hines Boulevard, Dallas, TX 75235-9063, USA.
FAU - Felner, E
AU  - Felner E
FAU - White, P C
AU  - White PC
LA  - eng
GR  - R37 DK37867/DK/NIDDK NIH HHS/United States
PT  - Case Reports
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Hum Mol Genet
JT  - Human molecular genetics
JID - 9208958
RN  - 0 (Neurophysins)
RN  - 11000-17-2 (Vasopressins)
RN  - 113-79-1 (Arginine Vasopressin)
SB  - IM
MH  - Arginine Vasopressin/genetics/physiology
MH  - Child
MH  - Child, Preschool
MH  - Diabetes Insipidus/*genetics/metabolism
MH  - Female
MH  - Genes, Recessive
MH  - Humans
MH  - Male
MH  - Mutation
MH  - Neurophysins/genetics
MH  - Sequence Analysis, DNA
MH  - Vasopressins/*genetics/metabolism
EDAT- 1999/06/17 00:00
MHDA- 1999/06/17 00:01
CRDT- 1999/06/17 00:00
PHST- 1999/06/17 00:00 [pubmed]
PHST- 1999/06/17 00:01 [medline]
PHST- 1999/06/17 00:00 [entrez]
AID - ddc146 [pii]
AID - 10.1093/hmg/8.7.1303 [doi]
PST - ppublish
SO  - Hum Mol Genet. 1999 Jul;8(7):1303-7. doi: 10.1093/hmg/8.7.1303.