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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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
Digital Object Identifier (DOI): doi:10.1016/j.nmd.2007.03.012
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
ePrint ID: 59937
Accepted Date and Publication Date:
August 2007Published
Date Deposited: 05 Sep 2008
Last Modified: 31 Mar 2016 12:42

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