caa a22 4500 397575165 CHVBK 20180308164853.0 cr unu---uuuuu 161202e199601 xx s 000 0 eng 10.1093/hmg/5.1.81 doi (NATIONALLICENCE)oxford-10.1093/hmg/5.1.81 Characterization of a Nonsense Mutation in the Ceruloplasmin Gene Resulting in Diabetes and Neurodegenerative Disease [Elektronische Daten] [Yoshitomo Takahashi, Hiroaki Miyajima, Susumu Shirabe, Shigenobu Nagataki, Akihito Suenaga, Jonathan D. 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. © 1996 Oxford University Press Takahashi Yoshitomo First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan aut Miyajima Hiroaki First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan aut Shirabe Susumu First Department of Medicine, Nagasaki University School of Medicine, Nagasaki, Japan aut Nagataki Shigenobu First Department of Medicine, Nagasaki University School of Medicine, Nagasaki, Japan aut Suenaga Akihito First Department of Medicine, Nagasaki University School of Medicine, Nagasaki, Japan aut Gitlin Jonathan D. Edward Mallinckrodt Department of Pediatrics, Washington University School of Medicine, St Louis, MO, USA aut Human Molecular Genetics Oxford University Press 5/1(1996-01), 81-84 0964-6906 5:1<81 1996 5 hmg https://doi.org/10.1093/hmg/5.1.81 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1093/hmg/5.1.81 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Takahashi Yoshitomo First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan aut NATIONALLICENCE 700 1- Miyajima Hiroaki First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan aut NATIONALLICENCE 700 1- Shirabe Susumu First Department of Medicine, Nagasaki University School of Medicine, Nagasaki, Japan aut NATIONALLICENCE 700 1- Nagataki Shigenobu First Department of Medicine, Nagasaki University School of Medicine, Nagasaki, Japan aut NATIONALLICENCE 700 1- Suenaga Akihito First Department of Medicine, Nagasaki University School of Medicine, Nagasaki, Japan aut NATIONALLICENCE 700 1- Gitlin Jonathan D. Edward Mallinckrodt Department of Pediatrics, Washington University School of Medicine, St Louis, MO, USA aut NATIONALLICENCE 773 0- Human Molecular Genetics Oxford University Press 5/1(1996-01), 81-84 0964-6906 5:1<81 1996 5 hmg Metadata rights reserved CC BY-NC-4.0 http://creativecommons.org/licenses/by-nc/4.0 nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-oxford