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


CONCLUSIONS
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.
Wolf
M T F
MT
Klinik für Kinder und Jugendliche, University of Erlangen-Nürnberg, Erlangen, Germany. matwolf@umich.edu
Dötsch
J
J
Metzler
M
M
Holder
M
M
Repp
R
R
Rascher
W
W
D000293:Adolescent; D000328:Adult; D000368:Aged; D001127:Arginine Vasopressin / Q000235:genetics*; D001483:Base Sequence; D002648:Child; D020790:Diabetes Insipidus, Neurogenic / Q000235:genetics*; D005260:Female; D006580:Genetic Carrier Screening; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D009481:Neurophysins / Q000235:genetics*; D010375:Pedigree
D009481:Neurophysins; D001127:Arginine Vasopressin