Abstract | BACKGROUND: MATERIAL AND METHODS: Here, we report the identification, clinical characterization, and in silico analysis of a novel compound heterozygosity in the ceruloplasmin gene of a 31-year-old man with iron overload. RESULTS: Increased serum ferritin levels, elevated iron saturation, as well as results of iron quantification in the liver and magnetic resonance imaging-based measurement of T2 relaxation times of the substantia nigra consistently suggested iron overload. By sequencing the ceruloplasmin gene, so far unknown nucleotide replacements G229C, and C2131A were detected in exons 2 and 12, respectively. In silico analyses showed that the resulting amino acid changes Asp58His and Gln692Lys are located at highly conserved positions. The Asp58His mutation is located on the surface of the protein, alters polarity, and may interfere with copper incorporation or ceruloplasmin trafficking. The Gln692Lys mutation is mapped to a beta-strand of domain 4 and may lead to conformational change of the cupredoxin fold. CONCLUSIONS:
|
Authors | Wolf Peter Hofmann, Christoph Welsch, Yoshitomo Takahashi, Hiroaki Miyajima, Ulrike Mihm, Christoph Krick, Stefan Zeuzem, Christoph Sarrazin |
Journal | Scandinavian journal of gastroenterology
(Scand J Gastroenterol)
Vol. 42
Issue 9
Pg. 1088-94
(Sep 2007)
ISSN: 0036-5521 [Print] England |
PMID | 17710675
(Publication Type: Case Reports, Journal Article)
|
Chemical References |
- Copper
- Ferritins
- Ceruloplasmin
|
Topics |
- Adult
- Brain
(pathology)
- Ceruloplasmin
(deficiency, genetics)
- Copper
(metabolism)
- Ferritins
(blood)
- Humans
- Iron Overload
(diagnosis, metabolism)
- Magnetic Resonance Imaging
- Male
- Mutation, Missense
(genetics)
- Neurodegenerative Diseases
(etiology, genetics)
- Point Mutation
(genetics)
- Sequence Alignment
|