MCID: GNT009
MIFTS: 52

Giant Axonal Neuropathy

Categories: Rare diseases, Genetic diseases, Neuronal diseases

Aliases & Classifications for Giant Axonal Neuropathy

MalaCards integrated aliases for Giant Axonal Neuropathy:

Name: Giant Axonal Neuropathy 23 50 24 25 51 29
Gan 50 24 25
Giant Axonal Neuropathy 1 50 69
Neuropathy, Giant Axonal 50 52
Giant Axonal Disease 25
Gan1 50

Classifications:



Summaries for Giant Axonal Neuropathy

NINDS : 51 Giant axonal neuropathy (GAN) is a rare inherited genetic disorder that affects both the central and peripheral nervous systems.  The majority of children with GAN will begin to show symptoms of the disease sometime before five years of age.  Signs of GAN usually begin in the peripheral nervous system, which controls movement and sensation in the arms, legs, and other parts of the body.  The typical symptoms of GAN are clumsiness and muscle weakness that progresses from a “waddling gait” to a pronounced difficulty in walking.  Additional symptoms include numbness or lack of feeling in the arms and legs, seizures, nystagmus (rapid back and forth movement of the eyes), and impaired cognitive development.  A characteristic sign of the disease is dull, tightly curled hair that is markedly different from the parents’ in color and texture. Researchers have discovered more than 20 different mutations associated with GAN in a gene, GAN1, which makes a protein called gigaxonin.   These mutations disrupt the regulation or production of gigaxonin in the nervous system.  As a result, axons, which are the long tails of neurons that allow them to communicate with other nerve cells, swell up with tangled filaments and become abnormally large.  Eventually these axons deteriorate and cause problems with movement and sensation since neurons are no longer able to communicate with each other.  Doctors diagnose GAN by using several tests, including one that measures nerve conduction velocity, a brain MRI, and a peripheral nerve biopsy (in which a bit of tissue from a peripheral nerve is removed and examined to look for swollen axons).  A definitive diagnosis using genetic testing is available on a research basis only.  GAN is inherited in an autosomal recessive pattern, which means that both parents of a child with GAN have to carry a copy of the mutated gene.   Parents, typically, will show no signs of the disease. 

MalaCards based summary : Giant Axonal Neuropathy, also known as gan, is related to giant axonal neuropathy 2, autosomal dominant and giant axonal neuropathy 2, and has symptoms including intellectual disability, spasticity and areflexia. An important gene associated with Giant Axonal Neuropathy is GAN (Gigaxonin), and among its related pathways/superpathways are Proteoglycans in cancer and Platelet activation. The drugs Simvastatin and Anticholesteremic Agents have been mentioned in the context of this disorder. Affiliated tissues include brain, spinal cord and testes, and related phenotypes are Increased number of mitotic cells and muscle

Genetics Home Reference : 25 Giant axonal neuropathy is an inherited condition characterized by abnormally large and dysfunctional axons called giant axons. Axons are specialized extensions of nerve cells (neurons) that transmit nerve impulses. Symptoms of the disorder first become apparent in the peripheral nervous system, in which long axons connect the brain and spinal cord (central nervous system) to muscles and to sensory cells that detect sensations such as touch, pain, heat, and sound. However, axons in the central nervous system are affected as well.

NIH Rare Diseases : 50 giant axonal neuropathy (gan) is a neurodegenerative disorder characterized by abnormally large and dysfunctional axons (the specialized extensions of nerve cells that are required for the transmission of nerve impulses). the condition typically appears in infancy or early childhood with severe peripheral motor and sensory neuropathy (affecting movement and sensation in the arms and legs). early signs include difficulty walking, lack of coordination, and loss of strength. over time, the central nervous system (brain and spinal cord) becomes involved, causing a gradual decline in mental function, loss of control of body movements, and seizures. giant axonal neuropathy is caused by mutations in the gan gene. it follows and autosomal dominant pattern of inheritance. management is directed by a multidisciplinary team with the goal of optimizing intellectual and physical development. last updated: 6/18/2015

Wikipedia : 72 Giant axonal neuropathy is a rare, autosomal recessive neurological disorder that causes disorganization... more...

GeneReviews: NBK1136

Related Diseases for Giant Axonal Neuropathy

Graphical network of the top 20 diseases related to Giant Axonal Neuropathy:



Diseases related to Giant Axonal Neuropathy

Symptoms & Phenotypes for Giant Axonal Neuropathy

Human phenotypes related to Giant Axonal Neuropathy:

32 (show all 26)
id Description HPO Frequency HPO Source Accession
1 intellectual disability 32 frequent (33%) HP:0001249
2 spasticity 32 frequent (33%) HP:0001257
3 areflexia 32 hallmark (90%) HP:0001284
4 generalized hypotonia 32 hallmark (90%) HP:0001290
5 abnormality of the cerebellum 32 frequent (33%) HP:0001317
6 joint hypermobility 32 hallmark (90%) HP:0001382
7 pes cavus 32 frequent (33%) HP:0001761
8 talipes equinovarus 32 frequent (33%) HP:0001762
9 woolly hair 32 frequent (33%) HP:0002224
10 pili canaliculi 32 hallmark (90%) HP:0002235
11 unsteady gait 32 frequent (33%) HP:0002317
12 difficulty walking 32 hallmark (90%) HP:0002355
13 distal muscle weakness 32 frequent (33%) HP:0002460
14 falls 32 occasional (7.5%) HP:0002527
15 scoliosis 32 frequent (33%) HP:0002650
16 genu valgum 32 occasional (7.5%) HP:0002857
17 distal sensory impairment 32 frequent (33%) HP:0002936
18 diffuse axonal swelling 32 hallmark (90%) HP:0003405
19 cns hypomyelination 32 hallmark (90%) HP:0003429
20 babinski sign 32 occasional (7.5%) HP:0003487
21 limb muscle weakness 32 occasional (7.5%) HP:0003690
22 proximal muscle weakness 32 hallmark (90%) HP:0003701
23 abnormality of the achilles tendon 32 hallmark (90%) HP:0005109
24 abnormal hand morphology 32 frequent (33%) HP:0005922
25 facial palsy 32 frequent (33%) HP:0010628
26 abnormality of the pituitary gland 32 occasional (7.5%) HP:0012503

UMLS symptoms related to Giant Axonal Neuropathy:


neuralgia, abnormal pyramidal signs, facial paresis

GenomeRNAi Phenotypes related to Giant Axonal Neuropathy according to GeneCards Suite gene sharing:

26
id Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Increased number of mitotic cells GR00098-A-3 8.8 CCT2 CCT7 TUBB

MGI Mouse Phenotypes related to Giant Axonal Neuropathy:

44
id Description MGI Source Accession Score Top Affiliating Genes
1 muscle MP:0005369 9.1 ACTG1 ARHGEF1 ARHGEF12 BAG3 GAN VIM

Drugs & Therapeutics for Giant Axonal Neuropathy

Drugs for Giant Axonal Neuropathy (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 6)
id Name Status Phase Clinical Trials Cas Number PubChem Id
1
Simvastatin Approved Phase 1 79902-63-9 54454
2 Anticholesteremic Agents Phase 1
3 Antimetabolites Phase 1
4 Hydroxymethylglutaryl-CoA Reductase Inhibitors Phase 1
5 Hypolipidemic Agents Phase 1
6 Lipid Regulating Agents Phase 1

Interventional clinical trials:


id Name Status NCT ID Phase Drugs
1 Simvatstatin Used to Treat Pulmonary Hypertension Unknown status NCT00538044 Phase 1 simvastatin
2 Intrathecal Administration of scAAV9/JeT-GAN for the Treatment of Giant Axonal Neuropathy Recruiting NCT02362438 Phase 1 Intrathecal Delivery of scAAV9/JeT-GAN
3 Giant Axonal Neuropathy Natural History Study Terminated NCT01503125

Search NIH Clinical Center for Giant Axonal Neuropathy

Genetic Tests for Giant Axonal Neuropathy

Genetic tests related to Giant Axonal Neuropathy:

id Genetic test Affiliating Genes
1 Giant Axonal Neuropathy 29 24 GAN

Anatomical Context for Giant Axonal Neuropathy

MalaCards organs/tissues related to Giant Axonal Neuropathy:

39
Brain, Spinal Cord, Testes, Eye, Skin, Pituitary, Cerebellum

Publications for Giant Axonal Neuropathy

Articles related to Giant Axonal Neuropathy:

(show top 50) (show all 125)
id Title Authors Year
1
Giant axonal neuropathy alters the structure of keratin intermediate filaments in human hair. ( 28424304 )
2017
2
A review of gigaxonin mutations in giant axonal neuropathy (GAN) and cancer. ( 27023907 )
2016
3
Pili canaliculi as manifestation of giant axonal neuropathy. ( 28300918 )
2016
4
Intermediate filament aggregates cause mitochondrial dysmotility and increase energy demands in giant axonal neuropathy. ( 27000625 )
2016
5
Abnormal intermediate filament organization alters mitochondrial motility in giant axonal neuropathy fibroblasts. ( 26700320 )
2016
6
Autonomic nervous system involvement in the giant axonal neuropathy (GAN) KO mouse: implications for human disease. ( 27369358 )
2016
7
Kelch Domain of Gigaxonin Interacts with Intermediate Filament Proteins Affected in Giant Axonal Neuropathy. ( 26460568 )
2015
8
A mild case of giant axonal neuropathy without central nervous system manifestation. ( 26381321 )
2015
9
Giant axonal neuropathy-like disease in an Alexandrine parrot (Psittacula eupatria). ( 26330398 )
2015
10
The instability of the BTB-KELCH protein Gigaxonin causes Giant Axonal Neuropathy and constitutes a new penetrant and specific diagnostic test. ( 24758703 )
2014
11
Giant axonal neuropathy: An updated perspective on its pathology and pathogenesis. ( 24947478 )
2014
12
Giant axonal neuropathy: a rare inherited neuropathy with simple clinical clues. ( 25216920 )
2014
13
Recommendations to enable drug development for inherited neuropathies: Charcot-Marie-Tooth and Giant Axonal Neuropathy. ( 24860645 )
2014
14
The absence of curly hair is associated with a milder phenotype in Giant Axonal Neuropathy. ( 23890932 )
2014
15
Intermediate filament protein accumulation in motor neurons derived from giant axonal neuropathy iPSCs rescued by restoration of gigaxonin. ( 25398950 )
2014
16
Atypical giant axonal neuropathy arising from a homozygous mutation by uniparental isodisomy. ( 25040701 )
2014
17
Giant axonal neuropathy: a clinicoradiopathologic diagnosis. ( 24590247 )
2014
18
Giant Axonal Neuropathy. ( 25213662 )
2014
19
Measuring Disease Progression in Giant Axonal Neuropathy: Implications for Clinical Trial Design. ( 25186661 )
2014
20
Unusual Neuroimaging Findings in Two Families with Giant Axonal Neuropathy. ( 26693541 )
2014
21
Giant axonal neuropathy. ( 23931822 )
2013
22
A novel mutation in the GAN gene causes an intermediate form of giant axonal neuropathy in an Arab-Israeli family. ( 23332420 )
2013
23
Explaining intermediate filament accumulation in giant axonal neuropathy. ( 25003002 )
2013
24
Heterogeneity of axonal pathology in Chinese patients with giant axonal neuropathy. ( 24273072 )
2013
25
Giant axonal neuropathy caused by a novel compound heterozygous mutation in the gigaxonin gene. ( 23248352 )
2013
26
Restoration of cytoskeleton homeostasis after gigaxonin gene transfer for giant axonal neuropathy. ( 23316953 )
2013
27
Giant axonal neuropathy-associated gigaxonin mutations impair intermediate filament protein degradation. ( 23585478 )
2013
28
Giant axonal neuropathy diagnosed on skin biopsy. ( 24211141 )
2013
29
Proteomic analysis in giant axonal neuropathy: new insights into disease mechanisms. ( 22806374 )
2012
30
Involvement of the globus pallidus in giant axonal neuropathy. ( 23044025 )
2012
31
Clinicogenetical features of a Japanese patient with giant axonal neuropathy. ( 21356581 )
2012
32
BAG3 mutations: another cause of giant axonal neuropathy. ( 22734908 )
2012
33
Giant axonal neuropathy caused by compound heterozygosity for a maternally inherited microdeletion and a paternal mutation within the GAN gene. ( 20949505 )
2010
34
Application of autologous bone marrow stem cells in giant axonal neuropathy. ( 22301809 )
2010
35
Giant axonal neuropathy: a pictorial essay and review of literature. ( 24148344 )
2010
36
Spectrum of magnetic resonance imaging findings in a family with giant axonal neuropathy confirmed by genetic studies. ( 19439850 )
2009
37
Genome-wide screen identifies drug-induced regulation of the gene giant axonal neuropathy (Gan) in a mouse model of antiretroviral-induced painful peripheral neuropathy. ( 19398414 )
2009
38
Phenotypic variability in giant axonal neuropathy. ( 19231187 )
2009
39
Clinical and genetic studies in a Chinese family with giant axonal neuropathy. ( 19295179 )
2009
40
Clinical, pathological and molecular findings in two siblings with giant axonal neuropathy (GAN): report from India. ( 18595793 )
2008
41
Genotype-phenotype analysis in patients with giant axonal neuropathy. ( 18343115 )
2008
42
3T MR with diffusion tensor imaging and single-voxel spectroscopy in giant axonal neuropathy. ( 18581347 )
2008
43
Giant axonal neuropathy. ( 17256086 )
2007
44
Genotype-phenotype analysis in patients with giant axonal neuropathy (GAN). ( 17587580 )
2007
45
New mutations, genotype phenotype studies and manifesting carriers in giant axonal neuropathy. ( 17578852 )
2007
46
Alterations in lipid metabolism gene expression and abnormal lipid accumulation in fibroblast explants from giant axonal neuropathy patients. ( 17331252 )
2007
47
Anesthesia for a child with giant axonal neuropathy. ( 17181534 )
2007
48
Giant axonal neuropathy: diffusion-weighted imaging features of the brain. ( 17005115 )
2006
49
Giant axonal neuropathy in two siblings: clinical histopathological findings. ( 15696785 )
2005
50
Giant axonal neuropathy: clinical and genetic study in six cases. ( 15897506 )
2005

Variations for Giant Axonal Neuropathy

ClinVar genetic disease variations for Giant Axonal Neuropathy:

6
id Gene Variation Type Significance SNP ID Assembly Location
1 GAN NM_022041.3(GAN): c.1456G> A (p.Glu486Lys) single nucleotide variant Pathogenic rs119485088 GRCh37 Chromosome 16, 81399037: 81399037
2 GAN NM_022041.3(GAN): c.1447C> T (p.Gln483Ter) single nucleotide variant Pathogenic rs119485089 GRCh37 Chromosome 16, 81399028: 81399028
3 GAN GAN, 1-BP INS, 18A insertion Pathogenic
4 GAN NM_022041.3(GAN): c.601C> T (p.Arg201Ter) single nucleotide variant Pathogenic rs119485090 GRCh37 Chromosome 16, 81388328: 81388328
5 GAN NM_022041.3(GAN): c.1268T> C (p.Ile423Thr) single nucleotide variant Pathogenic rs119485091 GRCh37 Chromosome 16, 81398610: 81398610
6 GAN NM_022041.3(GAN): c.413G> A (p.Arg138His) single nucleotide variant Pathogenic rs119485092 GRCh37 Chromosome 16, 81388140: 81388140
7 GAN NM_022041.3(GAN): c.43C> A (p.Arg15Ser) single nucleotide variant Pathogenic rs119485093 GRCh37 Chromosome 16, 81348761: 81348761
8 GAN NM_022041.3(GAN): c.1429C> T (p.Arg477Ter) single nucleotide variant Pathogenic rs119485094 GRCh37 Chromosome 16, 81399010: 81399010
9 GAN NM_022041.3(GAN): c.505G> A (p.Glu169Lys) single nucleotide variant Pathogenic rs119485095 GRCh37 Chromosome 16, 81388232: 81388232
10 GAN NM_022041.3(GAN): c.851+1G> A single nucleotide variant Pathogenic rs747291494 GRCh38 Chromosome 16, 81357003: 81357003

Expression for Giant Axonal Neuropathy

Search GEO for disease gene expression data for Giant Axonal Neuropathy.

Pathways for Giant Axonal Neuropathy

Pathways related to Giant Axonal Neuropathy according to GeneCards Suite gene sharing:

id Super pathways Score Top Affiliating Genes
1 11.81 ACTG1 ARHGEF1 ARHGEF12
2 11.42 ACTG1 ARHGEF1 ARHGEF12
3 11.41 ACTG1 ARHGEF1 TUBB VIM
4
Show member pathways
11.17 ACTG1 TUBB VIM
5 10.76 ACTG1 VIM

GO Terms for Giant Axonal Neuropathy

Cellular components related to Giant Axonal Neuropathy according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 cytoskeleton GO:0005856 9.91 ACTG1 CARMIL1 GAN MAP1B TUBB VIM
2 microtubule GO:0005874 9.71 CCT2 CCT7 MAP1B TUBB
3 cytosol GO:0005829 9.7 ACTG1 ARHGEF1 ARHGEF12 BAG3 CARMIL1 CCT2
4 extracellular matrix GO:0031012 9.67 ACTG1 CCT2 TUBB VIM
5 filamentous actin GO:0031941 9.46 ACTG1 CARMIL1
6 cytoplasm GO:0005737 9.44 ACTG1 ARHGEF1 ARHGEF12 BAG3 BCLAF1 CARMIL1
7 cell body GO:0044297 9.43 CCT2 CCT7 TUBB
8 chaperonin-containing T-complex GO:0005832 9.32 CCT2 CCT7
9 zona pellucida receptor complex GO:0002199 9.16 CCT2 CCT7

Biological processes related to Giant Axonal Neuropathy according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 protein folding GO:0006457 9.58 BAG3 CCT2 CCT7
2 protein stabilization GO:0050821 9.54 BAG3 CCT2 CCT7
3 binding of sperm to zona pellucida GO:0007339 9.48 CCT2 CCT7
4 toxin transport GO:1901998 9.46 CCT2 CCT7
5 positive regulation of telomere maintenance via telomerase GO:0032212 9.43 CCT2 CCT7
6 movement of cell or subcellular component GO:0006928 9.33 ACTG1 TUBB VIM
7 positive regulation of telomerase RNA localization to Cajal body GO:1904874 9.32 CCT2 CCT7
8 cellular process GO:0009987 9.26 MAP1B TUBB
9 positive regulation of establishment of protein localization to telomere GO:1904851 8.96 CCT2 CCT7
10 positive regulation of protein localization to Cajal body GO:1904871 8.62 CCT2 CCT7

Molecular functions related to Giant Axonal Neuropathy according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 protein binding GO:0005515 9.77 ACTG1 ARHGEF1 ARHGEF12 BAG3 BCLAF1 CARMIL1
2 structural molecule activity GO:0005198 9.43 MAP1B TUBB VIM
3 protein binding involved in protein folding GO:0044183 9.16 CCT2 CCT7
4 structural constituent of cytoskeleton GO:0005200 8.8 ACTG1 TUBB VIM

Sources for Giant Axonal Neuropathy

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 MedGen
42 MeSH
43 MESH via Orphanet
44 MGI
46 NCI
47 NCIt
48 NDF-RT
51 NINDS
52 Novoseek
54 OMIM
55 OMIM via Orphanet
59 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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