Genotype-phenotype analysis in patients with giant axonal neuropathy (GAN)
Koop, Olga, Schirmacher, Anja, Nelis, Eva, Timmerman, Vincent, De Jonghe, Peter, Ringelstein, Bernd, Rasic, Vedrana M., Evrard, Philippe, Gärtner, Jutter, Claeys, Kristl G., Appenzeller, Silke, Rautenstrauss, Bernd, Huhne, Kathrin, Ramos-Arroyo, Maria A., Wörle, Helmut, Moilanen, Jukka S., Hammans, Simon and Kuhlenbäumer, Gregor (2007) Genotype-phenotype analysis in patients with giant axonal neuropathy (GAN). Neuromuscular Disorders, 17, (8), 624-630. (doi:10.1016/j.nmd.2007.03.012).
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Description/Abstract
Giant axonal neuropathy (GAN, MIM: 256850) is a devastating autosomal recessive disorder characterized by an early onset severe peripheral neuropathy, varying central nervous system involvement and strikingly frizzly hair. Giant axonal neuropathy is usually caused by mutations in the gigaxonin gene (GAN) but genetic heterogeneity has been demonstrated for a milder variant of this disease. Here, we report ten patients referred to us for molecular genetic diagnosis. All patients had typical clinical signs suggestive of giant axonal neuropathy. In seven affected individuals, we found disease causing mutations in the gigaxonin gene affecting both alleles: two splice-site and four missense mutations, not reported previously. Gigaxonin binds N-terminally to ubiquitin activating enzyme E1 and C-terminally to various microtubule associated proteins causing their ubiquitin mediated degradation. It was shown for a number of gigaxonin mutations that they impede this process leading to accumulation of microtubule associated proteins and there by impairing cellular functions
| Item Type: | Article |
|---|---|
| ISSNs: | 0960-8966 (print) |
| Related URLs: | |
| Keywords: | humans,adolescent, exons, neurology, germany, magnetic resonance imaging, research support, mutation, child, research, diagnosis, microtubule-associated proteins, male, report, genotype, female, genetics, genetic heterogeneity, alleles, patients, peripheral nervous system diseases, phenotype, analysis, pathology, human, metabolism, promoter regions (genetics), dna mutational analysis, disease, proteins, protein, ubiquitin, cytoskeletal proteins, adult |
| Subjects: | R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry Q Science > QR Microbiology |
| Divisions: | University Structure - Pre August 2011 > School of Medicine > Human Genetics |
| Item ID: | 59937 |
| Date Deposited: | 05 Sep 2008 |
| Last Modified: | 01 Jun 2011 09:41 |
| Contributors: | Koop, Olga (Author) Schirmacher, Anja (Author) Nelis, Eva (Author) Timmerman, Vincent (Author) De Jonghe, Peter (Author) Ringelstein, Bernd (Author) Rasic, Vedrana M. (Author) Evrard, Philippe (Author) Gärtner, Jutter (Author) Claeys, Kristl G. (Author) Appenzeller, Silke (Author) Rautenstrauss, Bernd (Author) Huhne, Kathrin (Author) Ramos-Arroyo, Maria A. (Author) Wörle, Helmut (Author) Moilanen, Jukka S. (Author) Hammans, Simon (Author) Kuhlenbäumer, Gregor (Author) |
| Date: | August 2007 |
| Status: | Published |
| URI: | http://eprints.soton.ac.uk/id/eprint/59937 |
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