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Neuromuscul Disord. 2007 Aug;17(8):624-30. Epub 2007 Jun 22.

Genotype-phenotype analysis in patients with giant axonal neuropathy (GAN).

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  • 1Department of Neurology, University of Münster, Albert-Schweitzer Strasse 33, D-48129 Münster, Germany.

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.

PMID:
17587580
[PubMed - indexed for MEDLINE]
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