Giant axonal neuropathy: clinical and genetic study in six cases

Demir, Ercan

doi:10.1136/jnnp.2003.035162

Cited by 50 publications

(84 citation statements)

References 40 publications

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“…Our patients had normal mental status except for three. In EEG, disorganized background activity with focal spikes, spike-slow wave discharges, and paroxysmal slow wave activity were reported in literature [12,13]. None of our patients had seizures, we found not any EEG abnormalities in them.…”

Section: Discussionsupporting

confidence: 56%

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Giant axonal disease: Report of eight cases

İncecik

Hergüner

Ceylaner

et al. 2015

Brain and Development

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Section: Discussionsupporting

confidence: 56%

“…Mental deterioration was noted to start before the age of 10 years [2,12]. Our patients had normal mental status except for three.…”

Section: Discussionmentioning

confidence: 56%

Giant axonal disease: Report of eight cases

İncecik

Hergüner

Ceylaner

et al. 2015

Brain and Development

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“…5 Symptoms vary considerably. Frizzly hairs are not constant findings but appear to occur frequently.…”

Section: Discussionmentioning

confidence: 99%

Clinical and Genetic Studies in a Chinese Family With Giant Axonal Neuropathy

Zhang

Zou

2009

J Child Neurol

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The objective of the study was to investigate a girl with giant axonal neuropathy and detect the mutation of GAN gene in her family. The encoding exons of GAN gene were amplified from genomic DNA of the proband and her parents by polymerase chain reaction and directly sequenced after purification. The proband manifested typical neurological symptoms and pathological abnormalities. The case had 2 heterozygous missense mutations in GAN gene: 1. c. 224 T>A in exon 2, her mother was a heterozygote of this mutation and had normal phenotype; 2. c.1634G>A in exon 10, and her father was a heterozygote of this mutation and had normal phenotype. Both of the mutations caused amino acid changes in the gigaxonin protein. In this family, missense mutation of c.224 T>A and missense mutation of c.1634G>A in GAN gene caused the phenotype of giant axonal neuropathy in the proband. Her parents are heterozygotes of the disease without symptoms.

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“…Death normally occurs in the second or third decade of life. Peripheral nerve biopsies from humans show enlarged axons with densely packed and disorganized microtubules and intermediate filaments (IFs) (Demir et al, 2005;Nalini et al, 2008). The dysfunction and degeneration of peripheral nerves is attributed to this pathology.…”

Section: Introductionmentioning

confidence: 99%

“…More than 40 mutations have been identified in GAN patients, including deletions, insertions, missense and nonsense mutations, which lead to loss of function of gigaxonin (Bomont et al, 2000Bruno et al, 2004;Demir et al, 2005;Houlden et al, 2007;Koop et al, 2007;Kuhlenbä umer et al, 2002;Leung et al, 2007). Gigaxonin is a broadly expressed Cul3 ubiquitin ligase adaptor protein, normally present at extremely low levels throughout the brain (Cleveland et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Restoration of Cytoskeleton Homeostasis After Gigaxonin Gene Transfer for Giant Axonal Neuropathy

et al. 2013

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Giant axonal neuropathy (GAN) is caused by loss of function of the gigaxonin protein. On a cellular level GAN is characterized by intermediate filament (IF) aggregation, leading to a progressive and fatal peripheral neuropathy in humans. This study sought to determine if re-introduction of the GAN gene into GAN-deficient cells and mice would restore proper cytoskeleton IF homeostasis. Treatment of primary skin fibroblast cultures from three different GAN patients with an adeno-associated virus type 2 (AAV2) vector containing a normal human GAN transgene significantly reduced the number of cells displaying vimentin IF aggregates. A proteomic analysis of these treated cells was also performed, wherein the abundance of 32 of 780 identified proteins significantly changed in response to gigaxonin gene transfer. While 29 of these responding proteins have not been directly described in association with gigaxonin, three were previously identified as being disregulated in GAN and were now shifted toward normal levels. To assess the potential application of this approach in vivo and eventually in humans, GAN mice received an intracisternal injection of an AAV9/GAN vector to globally deliver the GAN gene to the brainstem and spinal cord. The treated mice showed a nearly complete clearance of peripherin IF accumulations at 3 weeks post-injection. These studies demonstrate that gigaxonin gene transfer can reverse the cellular IF aggregate pathology associated with GAN.

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Giant axonal neuropathy: clinical and genetic study in six cases

Cited by 50 publications

References 40 publications

Giant axonal disease: Report of eight cases

Giant axonal disease: Report of eight cases

Clinical and Genetic Studies in a Chinese Family With Giant Axonal Neuropathy

Restoration of Cytoskeleton Homeostasis After Gigaxonin Gene Transfer for Giant Axonal Neuropathy

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