Human Molecular Genetics, Vol 5, 81-84, Copyright © 1996 by Oxford University Press
Y Takahashi, H Miyajima, S Shirabe, S Nagataki, A Suenaga and JD Gitlin
We report here on the characterization of a mutation in the ceruloplasmin
gene in a 45 year old woman with insulin-dependent diabetes mellitus who
presented with the recent onset of gait disturbance and dysarthria.
Physical examination revealed an ataxic gait, scanning speech and retinal
degeneration. Magnetic resonance imaging of the brain was consistent with
increased basal ganglia iron content and laboratory studies revealed a low
serum iron concentration and no detectable serum ceruloplasmin. Nucleotide
sequence analysis of the ceruloplasmin gene from this patient revealed a G
to A substitution in exon 15 resulting in a nonsense mutation at amino acid
858 (Trp858ter). The patient's younger, neurologically asymptomatic brother
was also found to be homozygous for this mutation. Taken together the
clinical and genetic data support the concept of an essential and unique
role for ceruloplasmin in human iron metabolism. Identification of this
kindred extends the spectrum of ceruloplasmin gene mutations resulting in
this autosomal recessive, late-onset neurodegenerative disease and
highlights the importance of recognizing aceruloplasminemia as a genetic
cause of diabetes and neurologic disease.
ARTICLES
Characterization of a nonsense mutation in the ceruloplasmin gene resulting in diabetes and neurodegenerative disease
First Department of Medicine, Hamamatsu University School of Medicine, Japan.
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