GAN
MCID: GNT009
MIFTS: 44

Giant Axonal Neuropathy (GAN)

Categories: Cardiovascular diseases, Genetic diseases, Muscle diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Giant Axonal Neuropathy

MalaCards integrated aliases for Giant Axonal Neuropathy:

Name: Giant Axonal Neuropathy 25 20 43 53 36 29
Giant Axonal Neuropathy 1 20 70
Neuropathy, Giant Axonal 20 54
Gan 20 43
Giant Axonal Disease 43
Gan1 20

Classifications:



Summaries for Giant Axonal Neuropathy

MedlinePlus Genetics : 43 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.The signs and symptoms of giant axonal neuropathy generally begin in early childhood and get worse over time. Most affected individuals first have problems with walking. Later they may lose sensation, strength, and reflexes in their limbs; experience difficulty coordinating movements (ataxia); and require wheelchair assistance. Many affected individuals have an abnormal curvature of the spine (scoliosis). Visual and hearing problems may also occur. Many individuals with this condition have extremely kinky hair as compared to others in their family.Giant axonal neuropathy can also impact the autonomic nervous system, which controls involuntary body processes. Affected individuals may experience problems with constipation, heat intolerance, and the release of urine (neurogenic bladder), and a reduction in or loss of the ability to sweat.As the disorder worsens, paralysis, seizures, difficulty breathing or swallowing, and a gradual decline in mental function (dementia) can also occur. Most people with giant axonal neuropathy do not survive past their twenties.Some affected individuals have a milder form of giant axonal neuropathy that begins later in life. Movement problems in these individuals are less severe, and the signs and symptoms usually worsen at a slower rate than in the classic form of the condition. Individuals with the milder form often have straight hair, and they may survive into adulthood.

MalaCards based summary : Giant Axonal Neuropathy, also known as giant axonal neuropathy 1, is related to giant axonal neuropathy 2 and charcot-marie-tooth disease, axonal, type 2cc, and has symptoms including neuralgia, facial paresis and abnormal pyramidal signs. An important gene associated with Giant Axonal Neuropathy is GAN (Gigaxonin), and among its related pathways/superpathways are Cytoskeletal Signaling and Cytoskeleton remodeling Neurofilaments. Affiliated tissues include spinal cord, liver and bone, and related phenotypes are joint hypermobility and areflexia

GARD : 20 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.

NINDS : 53 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.

KEGG : 36 Giant axonal neuropathy is a disorder that shows giant axons, caused by accumulation of neurofilaments. Giant axonal neuropathy 1 (GAN1) is autosomal recessively inherited and caused by mutations in GAN (gigaxonin). GAN1 is characterized by an early onset severe peripheral neuropathy, varying central nervous system involvement and strikingly frizzly hair. Giant axonal neuropathy-2 (GAN2) is an autosomal dominant disorder, caused by mutations in DCAF8. GAN2 is characterized by distal sensory impairment and lower extremity muscle weakness and atrophy after the second decade.

Wikipedia : 73 Giant axonal neuropathy is a rare, autosomal recessive neurological disorder that causes disorganization... more...

GeneReviews: NBK1136

Related Diseases for Giant Axonal Neuropathy

Diseases in the Giant Axonal Neuropathy family:

Giant Axonal Neuropathy 1, Autosomal Recessive Giant Axonal Neuropathy 2, Autosomal Dominant
Giant Axonal Neuropathy 2

Diseases related to Giant Axonal Neuropathy via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 275)
# Related Disease Score Top Affiliating Genes
1 giant axonal neuropathy 2 32.0 NEFL GAN DCAF8 BAG3
2 charcot-marie-tooth disease, axonal, type 2cc 31.6 GAN DCAF8
3 axonal neuropathy 31.5 NEFL GAN DCAF8 BAG3
4 charcot-marie-tooth disease, axonal, type 2e 31.5 NEFL GAN DCAF8 BAG3
5 charcot-marie-tooth disease, type 4b2 31.3 NEFL GAN
6 neuropathy, congenital hypomyelinating, 1, autosomal recessive 31.1 NEFL GAN DCAF8
7 cohen syndrome 31.1 MAP1B GAN ALMS1
8 myopathy, myofibrillar, 6 30.2 DCAF8 BAG3
9 tooth disease 30.2 NEFL GAN BAG3 ACTG1
10 charcot-marie-tooth disease 30.0 NEFL GAN DCAF8 BAG3 ACTG1
11 giant axonal neuropathy 1, autosomal recessive 11.9
12 giant axonal neuropathy 2, autosomal dominant 11.8
13 retinitis pigmentosa 11.0
14 disease of mental health 11.0
15 hereditary spastic paraplegia 11.0
16 spastic paraplegia 76, autosomal recessive 10.9
17 neuropathy 10.9
18 spinal muscular atrophy, x-linked 2 10.8
19 charcot-marie-tooth disease, axonal, type 2p 10.8
20 ataxia-oculomotor apraxia 3 10.8
21 charcot-marie-tooth disease, axonal, type 2t 10.8
22 cold-induced sweating syndrome 10.8
23 alcoholic neuropathy 10.8
24 inflammatory and toxic neuropathy 10.8
25 neuromuscular disease 10.8
26 peripheral nervous system disease 10.6
27 overgrowth syndrome 10.5
28 polyneuropathy 10.5
29 autosomal recessive disease 10.5
30 triiodothyronine receptor auxiliary protein 10.5
31 ataxia and polyneuropathy, adult-onset 10.4
32 pathologic nystagmus 10.4
33 neuroaxonal dystrophy 10.3
34 hypotonia 10.3
35 hepatitis b 10.2
36 charcot-marie-tooth disease, axonal, type 2l 10.2 NEFL DCAF8
37 amyotrophic lateral sclerosis 1 10.2
38 neurodegeneration with brain iron accumulation 2a 10.2
39 alacrima, achalasia, and mental retardation syndrome 10.2
40 scoliosis 10.2
41 leukodystrophy 10.2
42 lateral sclerosis 10.2
43 sensory peripheral neuropathy 10.2
44 rapidly involuting congenital hemangioma 10.2
45 charcot-marie-tooth disease, demyelinating, type 1f 10.2 NEFL DCAF8
46 charcot-marie-tooth disease, axonal, type 2f 10.2 NEFL DCAF8
47 non-alcoholic fatty liver disease 10.2
48 irritable bowel syndrome 10.2
49 microvascular complications of diabetes 3 10.1
50 microvascular complications of diabetes 4 10.1

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:

31 (show all 26)
# Description HPO Frequency HPO Source Accession
1 joint hypermobility 31 hallmark (90%) HP:0001382
2 areflexia 31 hallmark (90%) HP:0001284
3 generalized hypotonia 31 hallmark (90%) HP:0001290
4 proximal muscle weakness 31 hallmark (90%) HP:0003701
5 difficulty walking 31 hallmark (90%) HP:0002355
6 abnormality of the achilles tendon 31 hallmark (90%) HP:0005109
7 cns hypomyelination 31 hallmark (90%) HP:0003429
8 diffuse axonal swelling 31 hallmark (90%) HP:0003405
9 pili canaliculi 31 hallmark (90%) HP:0002235
10 intellectual disability 31 frequent (33%) HP:0001249
11 spasticity 31 frequent (33%) HP:0001257
12 scoliosis 31 frequent (33%) HP:0002650
13 facial palsy 31 frequent (33%) HP:0010628
14 talipes equinovarus 31 frequent (33%) HP:0001762
15 pes cavus 31 frequent (33%) HP:0001761
16 abnormal cerebellum morphology 31 frequent (33%) HP:0001317
17 woolly hair 31 frequent (33%) HP:0002224
18 abnormal hand morphology 31 frequent (33%) HP:0005922
19 unsteady gait 31 frequent (33%) HP:0002317
20 distal muscle weakness 31 frequent (33%) HP:0002460
21 distal sensory impairment 31 frequent (33%) HP:0002936
22 genu valgum 31 occasional (7.5%) HP:0002857
23 babinski sign 31 occasional (7.5%) HP:0003487
24 limb muscle weakness 31 occasional (7.5%) HP:0003690
25 abnormality of the pituitary gland 31 occasional (7.5%) HP:0012503
26 falls 31 occasional (7.5%) HP:0002527

UMLS symptoms related to Giant Axonal Neuropathy:


neuralgia; facial paresis; abnormal pyramidal signs; cerebellar signs

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

26 (show all 17)
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Increased shRNA abundance (Z-score > 2) GR00366-A-105 9.58 VIM
2 Increased shRNA abundance (Z-score > 2) GR00366-A-126 9.58 NEFL
3 Increased shRNA abundance (Z-score > 2) GR00366-A-134 9.58 TUBB
4 Increased shRNA abundance (Z-score > 2) GR00366-A-156 9.58 TUBB
5 Increased shRNA abundance (Z-score > 2) GR00366-A-163 9.58 TUBB
6 Increased shRNA abundance (Z-score > 2) GR00366-A-176 9.58 TUBB
7 Increased shRNA abundance (Z-score > 2) GR00366-A-177 9.58 NEFL VIM
8 Increased shRNA abundance (Z-score > 2) GR00366-A-178 9.58 NEFL
9 Increased shRNA abundance (Z-score > 2) GR00366-A-189 9.58 VIM
10 Increased shRNA abundance (Z-score > 2) GR00366-A-198 9.58 NEFL
11 Increased shRNA abundance (Z-score > 2) GR00366-A-26 9.58 TUBB
12 Increased shRNA abundance (Z-score > 2) GR00366-A-29 9.58 TUBB
13 Increased shRNA abundance (Z-score > 2) GR00366-A-30 9.58 TUBB
14 Increased shRNA abundance (Z-score > 2) GR00366-A-5 9.58 NEFL
15 Increased shRNA abundance (Z-score > 2) GR00366-A-50 9.58 TUBB
16 Increased shRNA abundance (Z-score > 2) GR00366-A-63 9.58 VIM
17 Increased shRNA abundance (Z-score > 2) GR00366-A-70 9.58 TUBB

Drugs & Therapeutics for Giant Axonal Neuropathy

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 A Phase I Study of Intrathecal Administration of scAAV9/JeT-GAN for the Treatment of Giant Axonal Neuropathy Recruiting NCT02362438 Phase 1
2 Clinical Study of Giant Axonal Neuropathy Terminated NCT01503125

Search NIH Clinical Center for Giant Axonal Neuropathy

Genetic Tests for Giant Axonal Neuropathy

Genetic tests related to Giant Axonal Neuropathy:

# Genetic test Affiliating Genes
1 Giant Axonal Neuropathy 29

Anatomical Context for Giant Axonal Neuropathy

MalaCards organs/tissues related to Giant Axonal Neuropathy:

40
Spinal Cord, Liver, Bone, Heart, Cerebellum, Lung, Breast

Publications for Giant Axonal Neuropathy

Articles related to Giant Axonal Neuropathy:

(show top 50) (show all 218)
# Title Authors PMID Year
1
Gigaxonin controls vimentin organization through a tubulin chaperone-independent pathway. 61 54 25
19168853 2009
2
Gene targeting of GAN in mouse causes a toxic accumulation of microtubule-associated protein 8 and impaired retrograde axonal transport. 25 61 54
16565160 2006
3
Gigaxonin-controlled degradation of MAP1B light chain is critical to neuronal survival. 25 54 61
16227972 2005
4
Gigaxonin interacts with tubulin folding cofactor B and controls its degradation through the ubiquitin-proteasome pathway. 61 54 25
16303566 2005
5
Identification of seven novel mutations in the GAN gene. 54 61 25
12655563 2003
6
The gene encoding gigaxonin, a new member of the cytoskeletal BTB/kelch repeat family, is mutated in giant axonal neuropathy. 61 25 54
11062483 2000
7
Giant axonal neuropathy-associated gigaxonin mutations impair intermediate filament protein degradation. 25 61
23585478 2013
8
Sensory-motor deficits and neurofilament disorganization in gigaxonin-null mice. 25 61
21486449 2011
9
Giant axonal neuropathy caused by compound heterozygosity for a maternally inherited microdeletion and a paternal mutation within the GAN gene. 25 61
20949505 2010
10
Modest loss of peripheral axons, muscle atrophy and formation of brain inclusions in mice with targeted deletion of gigaxonin exon 1. 25 61
18680552 2008
11
Giant axonal neuropathy: clinical and genetic study in six cases. 25 61
15897506 2005
12
Gigaxonin is associated with the Golgi and dimerises via its BTB domain. 25 61
15073534 2004
13
Clinical and molecular findings in patients with giant axonal neuropathy (GAN). 61 25
14718689 2004
14
Giant axonal neuropathy: MRS findings. 25 61
14569833 2003
15
Intermediate filament aggregation in fibroblasts of giant axonal neuropathy patients is aggravated in non dividing cells and by microtubule destabilization. 61 25
12668605 2003
16
Cerebral proton magnetic resonance spectroscopy of a patient with giant axonal neuropathy. 25 61
12536033 2003
17
Microtubule-associated protein 1B: a neuronal binding partner for gigaxonin. 61 25
12147674 2002
18
Giant axonal neuropathy (GAN): case report and two novel mutations in the gigaxonin gene. 61 25
11971098 2002
19
Charcot-Marie-Tooth 2-like presentation of an Algerian family with giant axonal neuropathy. 61 25
11053687 2000
20
Focal conduction block in n-hexane polyneuropathy. 61 25
9626263 1998
21
Giant axonal neuropathy with inherited multisystem degeneration in a Tunisian kindred. 25 61
2153943 1990
22
Giant axonal neuropathy: observations on a further patient. 25 61
2849642 1988
23
Immunocytochemical studies of intermediate filament aggregates and their relationship to microtubules in cultured skin fibroblasts from patients with giant axonal neuropathy. 61 25
6315439 1983
24
Giant axonal neuropathy. 25 61
4339350 1972
25
Giant axonal neuropathy--a unique case with segmental neurofilamentous masses. 25 61
5044004 1972
26
Altered intracellular localization and valosin-containing protein (p97 VCP) interaction underlie ATP7A-related distal motor neuropathy. 25
22210628 2012
27
ATP7A-related copper transport diseases-emerging concepts and future trends. 25
21221114 2011
28
Missense mutations in the copper transporter gene ATP7A cause X-linked distal hereditary motor neuropathy. 25
20170900 2010
29
Clinical and genetic studies in a Chinese family with giant axonal neuropathy. 61 54
19295179 2009
30
Onset of human cytomegalovirus replication in fibroblasts requires the presence of an intact vimentin cytoskeleton. 54 61
19403668 2009
31
Genome-wide screen identifies drug-induced regulation of the gene giant axonal neuropathy (Gan) in a mouse model of antiretroviral-induced painful peripheral neuropathy. 61 54
19398414 2009
32
Mutations in a BTB-Kelch protein, KLHL7, cause autosomal-dominant retinitis pigmentosa. 61 54
19520207 2009
33
Phenotypic variability in giant axonal neuropathy. 54 61
19231187 2009
34
Clinical, pathological and molecular findings in two siblings with giant axonal neuropathy (GAN): report from India. 61 54
18595793 2008
35
Genotype-phenotype analysis in patients with giant axonal neuropathy (GAN). 61 54
17587580 2007
36
PLA2G6, encoding a phospholipase A2, is mutated in neurodegenerative disorders with high brain iron. 25
16783378 2006
37
Microtubule-associated protein 1S, a short and ubiquitously expressed member of the microtubule-associated protein 1 family. 54 61
15528209 2005
38
Crystal structure of the Kelch domain of human Keap1. 25
15475350 2004
39
Targeting of protein ubiquitination by BTB-Cullin 3-Roc1 ubiquitin ligases. 25
14528312 2003
40
Genetic heterogeneity in giant axonal neuropathy: an Algerian family not linked to chromosome 16q24.1. 61 54
12398836 2002
41
The kelch repeat superfamily of proteins: propellers of cell function. 25
10603472 2000
42
Mutations in the peripheral myelin genes and associated genes in inherited peripheral neuropathies. 25
9888385 1999
43
Aggregation of a subpopulation of vimentin filaments in cultured human skin fibroblasts derived from patients with giant axonal neuropathy. 54 61
8635201 1996
44
Giant axonal neuropathy: studies with sulfhydryl donor compounds. 54 61
2324766 1990
45
Current Clinical Applications of In Vivo Gene Therapy with AAVs. 61
33309881 2021
46
Giant axonal neuropathy with novel GAN pathogenic variant in a patient of consanguineous origin from Poonch Jammu and Kashmir-India. 61
33528728 2021
47
Orphan Peripheral Neuropathies. 61
32986679 2021
48
Expanding the genotype-phenotype correlation of childhood sensory polyneuropathy of genetic origin. 61
32999401 2020
49
Postnatal Woolly Hair: A Key to Diagnosis in Giant Axonal Neuropathy. 61
32522339 2020
50
The rare Alus element-mediated chimerism of multiple de novo complex rearrangement sequences in GAN result in giant axonal neuropathy. 61
31877298 2020

Variations for Giant Axonal Neuropathy

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:

# Super pathways Score Top Affiliating Genes
1 11.84 VIM TUBB NEFL ARHGEF1 ACTG1
2
Show member pathways
10.96 VIM TUBB NEFL ACTG1
3 10.66 VIM ACTG1

GO Terms for Giant Axonal Neuropathy

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

# Name GO ID Score Top Affiliating Genes
1 cytoplasm GO:0005737 9.73 VIM TUBB NEFL MAP1B GAN DCAF8
2 growth cone GO:0030426 9.33 NEFL MAP1B APBB2
3 cytoskeleton GO:0005856 9.23 VIM TUBB NEFL MAP1B GAN ALMS1

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

# Name GO ID Score Top Affiliating Genes
1 microtubule cytoskeleton organization GO:0000226 9.54 TUBB NEFL MAP1B
2 spinal cord development GO:0021510 9.4 NEFL BAG3
3 intermediate filament organization GO:0045109 9.32 VIM NEFL
4 regulation of stress fiber assembly GO:0051492 9.26 ALMS1 ACTG1
5 postsynaptic actin cytoskeleton organization GO:0098974 9.16 ACTG1 ACTBL2
6 cellular process GO:0009987 8.96 TUBB MAP1B
7 peripheral nervous system axon regeneration GO:0014012 8.62 NEFL MAP1B

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

# Name GO ID Score Top Affiliating Genes
1 protein binding GO:0005515 10.1 VIM TUBB NEFL MAP1B GAN DCAF8
2 protein-containing complex binding GO:0044877 9.46 TUBB NEFL MAP1B BAG3
3 structural constituent of postsynaptic actin cytoskeleton GO:0098973 8.96 ACTG1 ACTBL2
4 structural constituent of cytoskeleton GO:0005200 8.92 VIM TUBB NEFL ACTG1

Sources for Giant Axonal Neuropathy

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 20-May-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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