NBIA2A
MCID: NRD033
MIFTS: 69

Neurodegeneration with Brain Iron Accumulation 2a (NBIA2A)

Categories: Eye diseases, Genetic diseases, Mental diseases, Metabolic diseases, Muscle diseases, Neuronal diseases, Rare diseases
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Aliases & Classifications for Neurodegeneration with Brain Iron Accumulation 2a

MalaCards integrated aliases for Neurodegeneration with Brain Iron Accumulation 2a:

Name: Neurodegeneration with Brain Iron Accumulation 2a 57 11 73 14
Infantile Neuroaxonal Dystrophy 19 42 52 58 73 28 5 71 75
Seitelberger Disease 57 11 19 42 58 73
Plan 57 24 19 58 73
Inad 57 19 42 58 73
Pla2g6-Associated Neurodegeneration 24 58 28 5
Infantile Neuroaxonal Dystrophy 1 57 11 73 12
Inad1 11 19 58 73
Neuroaxonal Dystrophy, Infantile 57 19 53
Nbia2a 57 11 73
Neurodegeneration with Brain Iron Accumulation, Pla2g6-Related 19 42
Phospholipase A2-Associated Neurodegeneration 19 58
Neurodegeneration, Pla2g6-Associated 57 11
Nbia, Pla2g6-Related 42 75
Infantile Neuroaxonal Dystrophy/atypical Neuroaxonal Dystrophy 19
Neurodegeneration, with Brain Iron Accumulation, Type 2a 38
Neurodegeneration with Brain Iron Accumulation 2b 19
Neurodegeneration with Brain Iron Accumulation 2 71
Neurodegeneration Pla2g6-Associated 73
Dystrophy, Neuroaxonal, Infantile 38
Neuroaxonal Dystrophy, Atypical 19
Pla2g6-Related Disorders 24
Karak Syndrome, Included 19
Neuroaxonal Dystrophies 71
Seitelberger's Disease 42
Nbia2b 19
Nbia2 24

Characteristics:


Inheritance:

Neurodegeneration with Brain Iron Accumulation 2a: Autosomal recessive 57
Infantile Neuroaxonal Dystrophy: Autosomal recessive 58

Age Of Onset:

Infantile Neuroaxonal Dystrophy: Infancy,Neonatal 58

OMIM®:

57 (Updated 08-Dec-2022)
Miscellaneous:
onset usually in infancy or up to 2 years of age although later onset has been reported ('late-infantile')
death usually by age 10 years
allelic disorder to neurodegeneration with brain iron accumulation 2b (nbia2b, )
phenotypic overlap with pkan neuroaxonal dystrophy (nbia1, )


Classifications:

Orphanet: 58  
Rare neurological diseases
Inborn errors of metabolism


Summaries for Neurodegeneration with Brain Iron Accumulation 2a

MedlinePlus Genetics: 42 Infantile neuroaxonal dystrophy is a disorder that primarily affects the nervous system. Individuals with infantile neuroaxonal dystrophy typically do not have any symptoms at birth, but between the ages of about 6 and 18 months they begin to experience delays in acquiring new motor and intellectual skills, such as crawling or beginning to speak. Eventually they lose previously acquired skills (developmental regression). In some cases, signs and symptoms of infantile neuroaxonal dystrophy first appear later in childhood or during the teenage years and progress more slowly.Children with infantile neuroaxonal dystrophy experience progressive difficulties with movement. They generally have muscles that are at first weak and "floppy" (hypotonic), and then gradually become very stiff (spastic). Eventually, affected children lose the ability to move independently. Lack of muscle strength causes difficulty with feeding. Muscle weakness can also result in breathing problems that can lead to frequent infections, such as pneumonia. Seizures occur in some affected children.Rapid, involuntary eye movements (nystagmus), eyes that do not look in the same direction (strabismus), and vision loss due to deterioration (atrophy) of the nerve that carries information from the eye to the brain (the optic nerve) often occur in infantile neuroaxonal dystrophy. Hearing loss may also develop. Children with this disorder experience progressive deterioration of cognitive functions (dementia), and they eventually lose awareness of their surroundings.Infantile neuroaxonal dystrophy is characterized by the development of swellings called spheroid bodies in the axons, the fibers that extend from nerve cells (neurons) and transmit impulses to muscles and other neurons. In some individuals with infantile neuroaxonal dystrophy, abnormal amounts of iron accumulate in a specific region of the brain called the basal ganglia. The relationship of these features to the symptoms of infantile neuroaxonal dystrophy is unknown.

MalaCards based summary: Neurodegeneration with Brain Iron Accumulation 2a, also known as infantile neuroaxonal dystrophy, is related to dementia, lewy body and parkinson disease 3, autosomal dominant, and has symptoms including ataxia, dysdiadochokinesis and gait ataxia. An important gene associated with Neurodegeneration with Brain Iron Accumulation 2a is PLA2G6 (Phospholipase A2 Group VI), and among its related pathways/superpathways are Metabolism and Glycerophospholipid biosynthesis. The drugs Desipramine and Neurotransmitter Agents have been mentioned in the context of this disorder. Affiliated tissues include brain, eye and skin, and related phenotypes are developmental regression and cerebellar atrophy

NINDS: 52 Infantile neuroaxonal dystrophy (INAD) is a rare inherited neurological disorder. It affects axons, the part of a nerve cell that carries messages from the brain to other parts of the body, and causes progressive loss of vision, muscular control, and mental skills. Mutations in the PLA2G6 gene have been identified in most individuals with infantile neuroaxonal dystrophy. While the basic genetic and metabolic causes are unknown, INAD is the result of an abnormal build-up of toxic substances in nerves that communicate with muscles, skin, and the conjunctive tissue around the eyes.  Symptoms usually begin within the first 2 years of life, with the loss of head control and the ability to sit, crawl, or walk, accompanied by deterioration in vision and speech.  Some children may have seizures.  Distinctive facial deformities may be present at birth, including a prominent forehead, crossed eyes, an unusually small nose or jaw, and large, low-set ears.  INAD is an autosomal recessive disorder, which means that both parents must be carriers of the defective gene that causes INAD to pass it on to their child. Electrophysiology (nerve conduction velocities) may be helpful for diagnosis, although diagnosis is usually confirmed by tissue biopsy of skin, rectum, nerve or conjunctive tissue to confirm the presence of characteristic swellings (spheroid bodies) in the nerve axons.

Orphanet: 58 Infantile neuroaxonal dystrophy/atypical neuroaxonal dystrophy (INAD/atypical NAD) is a type of neurodegeneration with brain iron accumulation (NBIA; see this term) characterized by psychomotor delay and regression, increasing neurological involvement with symmetrical pyramidal tract signs and spastic tetraplegia. INAD may be classic or atypical and patients present with symptoms anywhere along a continuum between the two.

OMIM®: 57 Neurodegeneration with brain iron accumulation-2A is an autosomal recessive neurodegenerative disease characterized by onset in the first 2 years of life; it is also referred to as infantile neuroaxonal dystrophy (INAD). Pathologic findings include axonal swelling and spheroid bodies in the central nervous system (review by Gregory et al., 2009). (256600) (Updated 08-Dec-2022)

GARD: 19 Infantile neuroaxonal dystrophy is a type of lipid storage disorder that mostly affects the nervous system. It has two forms, a classic form and an atypical form. Infantile neuroaxonal dystrophy is caused by changes (pathogenic variants) in the PLA2G6 gene and is inherited in an autosomal recessive pattern.

Disease Ontology: 11 A neurodegeneration with brain iron accumulation that has material basis in autosomal recessive inheritance of mutation in the PLA2G6 gene on chromosome 22q13.1 and is characterized by onset in the first 2 years of life.

UniProtKB/Swiss-Prot: 73 A neurodegenerative disease characterized by pathologic axonal swelling and spheroid bodies in the central nervous system. Onset is within the first 2 years of life with death by age 10 years.

Wikipedia: 75 Infantile neuroaxonal dystrophy is a rare pervasive developmental disorder that primarily affects the... more...

GeneReviews: NBK1675

Related Diseases for Neurodegeneration with Brain Iron Accumulation 2a

Diseases in the Neurodegeneration with Brain Iron Accumulation family:

Neurodegeneration with Brain Iron Accumulation 1 Neurodegeneration with Brain Iron Accumulation 2a
Neurodegeneration with Brain Iron Accumulation 5 Neurodegeneration with Brain Iron Accumulation 3
Neurodegeneration with Brain Iron Accumulation 2b Neurodegeneration with Brain Iron Accumulation 4
Neurodegeneration with Brain Iron Accumulation 6 Neurodegeneration with Brain Iron Accumulation 7
Neurodegeneration with Brain Iron Accumulation 8

Diseases related to Neurodegeneration with Brain Iron Accumulation 2a via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 1280)
# Related Disease Score Top Affiliating Genes
1 dementia, lewy body 30.9 RPS27A PLA2G6 ATP13A2 APP
2 parkinson disease 3, autosomal dominant 30.3 PLA2G6 ATP13A2
3 alcohol-related neurodevelopmental disorder 30.1 WDR45 PLA2G6 PANK2 C19orf12
4 cerebral degeneration 30.0 PLA2G6 PANK2 FA2H APP
5 parkinson disease 15, autosomal recessive early-onset 29.6 WDR45 PLA2G6 PANK2 FA2H C19orf12 ATP13A2
6 iron metabolism disease 29.5 PANK2 FTL CP
7 early-onset parkinson's disease 29.4 WDR45 PLA2G6 PANK2 FA2H DCAF17 COASY
8 parkinson disease 14, autosomal recessive 29.4 PNPLA8 PLA2G6
9 supranuclear palsy, progressive, 1 29.1 RPS27A ATP13A2 APP
10 hereditary spastic paraplegia 29.1 WDR45 PLA2G6 PANK2 PANK1 FA2H DCAF17
11 parkinson disease, late-onset 29.0 RPS27A PLA2G6 CP ATP13A2 APP
12 autosomal dominant cerebellar ataxia 28.9 RPS27A ATP13A2 APP
13 neuronal ceroid lipofuscinosis 28.9 PLA2G6 PANK2 NAGA C19orf12 ATP13A2 APP
14 parkinsonism 28.0 WDR45 RPS27A PLA2G6 PANK2 FTL COASY
15 movement disease 27.8 WDR45 RPS27A PLA2G6 PANK2 PANK1 FTL
16 neurodegeneration with brain iron accumulation 1 27.7 WDR45 PLA2G6 PANK2 PANK1 FTL FA2H
17 dystonia 27.7 WDR45 PLA2G6 PANK2 PANK1 FTL FA2H
18 neurodegeneration with brain iron accumulation 2b 27.5 WDR45 PNPLA2 PLA2G6 PLA2G1B PANK2 PANK1
19 neurodegeneration with brain iron accumulation 27.1 WDR45 PNPLA2 PLA2G6 PLA2G1B PANK2 PANK1
20 neuroaxonal dystrophy 26.9 WDR45 PNPLA8 PNPLA2 PLA2G6 PLA2G1B PANK2
21 aceruloplasminemia 26.6 WDR45 PLA2G6 PLA2G1B PANK2 PANK1 FTL
22 osteopetrosis and infantile neuroaxonal dystrophy 11.4
23 osteopetrosis, autosomal recessive 5 11.3
24 csf1r-related brain malformation and osteopetrosis 11.3
25 schindler disease, type i 11.3
26 spastic paraplegia 35, autosomal recessive, with or without neurodegeneration 11.2
27 lupus erythematosus 11.2
28 asthma 11.1
29 stuttering 11.1
30 prediabetes syndrome 11.1
31 chronic fatigue syndrome 11.0
32 aplastic anemia 11.0
33 dementia 11.0
34 pulmonary disease, chronic obstructive 11.0
35 diabetes mellitus 11.0
36 alcohol use disorder 11.0
37 hypertension, essential 11.0
38 kidney disease 10.9
39 type 2 diabetes mellitus 10.9
40 cerebral palsy 10.9
41 hypoglycemia 10.9
42 typhoid fever 10.9
43 ovarian cancer 10.9
44 fibromyalgia 10.9
45 fetal alcohol syndrome 10.9
46 leukoencephalopathy, hereditary diffuse, with spheroids 1 10.9
47 smith-lemli-opitz syndrome 10.9
48 cerebellar ataxia, deafness, and narcolepsy, autosomal dominant 10.9
49 spinocerebellar ataxia 36 10.9
50 ceroid lipofuscinosis, neuronal, 11 10.9

Graphical network of the top 20 diseases related to Neurodegeneration with Brain Iron Accumulation 2a:



Diseases related to Neurodegeneration with Brain Iron Accumulation 2a

Symptoms & Phenotypes for Neurodegeneration with Brain Iron Accumulation 2a

Human phenotypes related to Neurodegeneration with Brain Iron Accumulation 2a:

58 30 (show top 50) (show all 75)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 developmental regression 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0002376
2 cerebellar atrophy 58 30 Very rare (1%) Very frequent (99-80%)
HP:0001272
3 psychomotor deterioration 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0002361
4 hyperreflexia 58 30 Frequent (33%) Frequent (79-30%)
HP:0001347
5 abnormal pyramidal sign 58 30 Frequent (33%) Frequent (79-30%)
HP:0007256
6 ataxia 58 30 Very rare (1%) Frequent (79-30%)
HP:0001251
7 optic atrophy 58 30 Very rare (1%) Frequent (79-30%)
HP:0000648
8 abnormality of peripheral nerve conduction 58 30 Frequent (33%) Frequent (79-30%)
HP:0003134
9 abnormality of visual evoked potentials 58 30 Frequent (33%) Frequent (79-30%)
HP:0000649
10 bulbar signs 58 30 Frequent (33%) Frequent (79-30%)
HP:0002483
11 progressive spasticity 58 30 Frequent (33%) Frequent (79-30%)
HP:0002191
12 spastic tetraparesis 58 30 Frequent (33%) Frequent (79-30%)
HP:0001285
13 abnormal cerebral white matter morphology 58 30 Frequent (33%) Frequent (79-30%)
HP:0002500
14 unsteady gait 58 30 Frequent (33%) Frequent (79-30%)
HP:0002317
15 peripheral axonal neuropathy 58 30 Frequent (33%) Frequent (79-30%)
HP:0003477
16 sensorimotor neuropathy 58 30 Frequent (33%) Frequent (79-30%)
HP:0007141
17 emg: chronic denervation signs 58 30 Very rare (1%) Frequent (79-30%)
HP:0003444
18 diffuse axonal swelling 58 30 Frequent (33%) Frequent (79-30%)
HP:0003405
19 cerebellar gliosis 58 30 Frequent (33%) Frequent (79-30%)
HP:0012698
20 eye of the tiger anomaly of globus pallidus 30 Frequent (33%) HP:0002454
21 increased circulating lactate dehydrogenase concentration 30 Frequent (33%) HP:0025435
22 axial hypotonia 30 Frequent (33%) HP:0008936
23 emotional lability 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0000712
24 dysarthria 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0001260
25 constipation 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0002019
26 delayed speech and language development 58 30 Very rare (1%) Occasional (29-5%)
HP:0000750
27 blindness 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0000618
28 flexion contracture 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0001371
29 strabismus 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0000486
30 dystonia 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0001332
31 aspiration pneumonia 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0011951
32 autistic behavior 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0000729
33 hyperactivity 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0000752
34 impulsivity 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0100710
35 short attention span 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0000736
36 temperature instability 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0005968
37 drooling 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0002307
38 abnormal autonomic nervous system physiology 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0012332
39 pendular nystagmus 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0012043
40 seizure 58 30 Very rare (1%) Very rare (<4-1%)
HP:0001250
41 iron accumulation in brain 58 30 Very rare (1%) Frequent (79-30%)
HP:0012675
42 choking episodes 58 30 Very rare (1%) Very rare (<4-1%)
HP:0030842
43 apneic episodes in infancy 58 30 Very rare (1%) Very rare (<4-1%)
HP:0005949
44 upgaze palsy 58 30 Very rare (1%) Very rare (<4-1%)
HP:0025331
45 downbeat nystagmus 58 30 Very rare (1%) Very rare (<4-1%)
HP:0010545
46 vegetative state 58 30 Very rare (1%) Very rare (<4-1%)
HP:0031358
47 decreased nerve conduction velocity 30 Very rare (1%) HP:0000762
48 cerebral atrophy 30 Very rare (1%) HP:0002059
49 impaired social interactions 30 Very rare (1%) HP:0000735
50 gliosis 30 Very rare (1%) HP:0002171

Symptoms via clinical synopsis from OMIM®:

57 (Updated 08-Dec-2022)
Neurologic Central Nervous System:
ataxia
hypotonia
spastic tetraplegia
cerebellar atrophy
cerebral atrophy
more
Laboratory Abnormalities:
characteristic spheroids can be found in peripheral tissue, such as skin and conjunctiva

Neurologic Peripheral Nervous System:
chronic denervation seen on emg
axonal dystrophy
axonal swelling or thickening
axonal 'spheroid' inclusions
decreased nerve conduction velocities (ncv) (30%)

Clinical features from OMIM®:

256600 (Updated 08-Dec-2022)

UMLS symptoms related to Neurodegeneration with Brain Iron Accumulation 2a:


ataxia; dysdiadochokinesis; gait ataxia; bradykinesia; action tremor; seizures; muscle spasticity; cerebellar ataxia; weakness; abnormal pyramidal signs

MGI Mouse Phenotypes related to Neurodegeneration with Brain Iron Accumulation 2a:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 homeostasis/metabolism MP:0005376 10.1 APP ATP13A2 COASY CP FA2H FTL
2 growth/size/body region MP:0005378 9.9 APP COASY CP FTL PANK1 PANK2
3 cellular MP:0005384 9.7 APP ATP13A2 COASY CP DCAF17 PANK1
4 behavior/neurological MP:0005386 9.36 APP ATP13A2 COASY CP FA2H FTL

Drugs & Therapeutics for Neurodegeneration with Brain Iron Accumulation 2a

Drugs for Neurodegeneration with Brain Iron Accumulation 2a (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 8)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Desipramine Approved, Investigational Phase 4 50-47-5 2995
2 Neurotransmitter Agents Phase 4
3 Adrenergic Agents Phase 4
4 Psychotropic Drugs Phase 4
5 Antidepressive Agents, Tricyclic Phase 4
6 Antidepressive Agents Phase 4
7 Linoleate Phase 2, Phase 3
8
Iron Approved 7439-89-6 29936

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Novel Off-label Use of Desipramine in Infantile Neuroaxonal Dystrophy: Targeting the Sphingolipid Metabolism Pathway to Reduce Accumulation of Ceramide. Terminated NCT03726996 Phase 4 Desipramine
2 A Prospective Open-label Study to Assess Efficacy and Safety of RT001 in Subjects With Infantile Neuroaxonal Dystrophy Active, not recruiting NCT03570931 Phase 2, Phase 3 RT001
3 A Retrospective Review of the Natural History of Infantile Neuroaxonal Dystrophy Completed NCT03999814
4 Protocol RT001-009: A Natural History Study of Infantile Neuroaxonal Dystrophy Completed NCT04027816
5 TIRCON International NBIA (Neurodegeneration Associated With Brain Iron Accumulation) Patient Registry and Natural History Study Recruiting NCT05522374
6 Phenotypic Description of Patients With Atypical Clinical Forms of PLA2G6 Mutations Enrolling by invitation NCT05440994

Search NIH Clinical Center for Neurodegeneration with Brain Iron Accumulation 2a

Genetic Tests for Neurodegeneration with Brain Iron Accumulation 2a

Genetic tests related to Neurodegeneration with Brain Iron Accumulation 2a:

# Genetic test Affiliating Genes
1 Infantile Neuroaxonal Dystrophy 28 PLA2G6
2 Pla2g6-Associated Neurodegeneration 28

Anatomical Context for Neurodegeneration with Brain Iron Accumulation 2a

Organs/tissues related to Neurodegeneration with Brain Iron Accumulation 2a:

MalaCards : Brain, Eye, Skin, Globus Pallidus, Prostate, Cortex, Caudate Nucleus
ODiseA: Brain-Cortex, Brain, Brain-Basal Ganglia, Brain-Basal Ganglia-Caudate Nucleus, Brain-Basal Ganglia-Putamen

Publications for Neurodegeneration with Brain Iron Accumulation 2a

Articles related to Neurodegeneration with Brain Iron Accumulation 2a:

(show top 50) (show all 30419)
# Title Authors PMID Year
1
Novel splice-site mutations and a large intragenic deletion in PLA2G6 associated with a severe and rapidly progressive form of infantile neuroaxonal dystrophy. 62 24 57 5
20584031 2010
2
Neurodegeneration associated with genetic defects in phospholipase A(2). 62 24 57 5
18799783 2008
3
PLA2G6, encoding a phospholipase A2, is mutated in neurodegenerative disorders with high brain iron. 62 24 57 5
16783378 2006
4
PLA2G6 mutation underlies infantile neuroaxonal dystrophy. 62 57 5
17033970 2006
5
Validation of the finding of hypertrophy of the clava in infantile neuroaxonal dystrophy/PLA2G6 by biometric analysis. 62 24 5
27516098 2016
6
PLA2G6-associated Dystonia-Parkinsonism: Case Report and Literature Review. 62 24 5
26196026 2015
7
Infantile and childhood onset PLA2G6-associated neurodegeneration in a large North African cohort. 62 24 5
25164370 2015
8
PLA2G6-associated neurodegeneration (PLAN): further expansion of the clinical, radiological and mutation spectrum associated with infantile and atypical childhood-onset disease. 62 24 5
24745848 2014
9
Widespread Lewy body and tau accumulation in childhood and adult onset dystonia-parkinsonism cases with PLA2G6 mutations. 62 24 5
20619503 2012
10
Catalytic function of PLA2G6 is impaired by mutations associated with infantile neuroaxonal dystrophy but not dystonia-parkinsonism. 62 24 5
20886109 2010
11
Multiplex ligation-dependent probe amplification (MLPA) analysis is an effective tool for the detection of novel intragenic PLA2G6 mutations: implications for molecular diagnosis. 62 24 5
20226704 2010
12
Characterization of PLA2G6 as a locus for dystonia-parkinsonism. 62 24 5
18570303 2009
13
Infantile neuroaxonal dystrophy: neuroradiological studies in 11 patients. 62 24 57
10379598 1999
14
Infantile neuroaxonal dystrophy: clinical spectrum and diagnostic criteria. 62 24 57
10227637 1999
15
Early-onset L-dopa-responsive parkinsonism with pyramidal signs due to ATP13A2, PLA2G6, FBXO7 and spatacsin mutations. 24 5
20669327 2010
16
PLA2G6-associated neurodegeneration: New insights into brain abnormalities and disease progression. 62 5
30340910 2019
17
Identification of Novel Compound Mutations in PLA2G6-Associated Neurodegeneration Patient with Characteristic MRI Imaging. 62 5
27395053 2017
18
Child Neurology: Two sisters with dystonia and regression: PLA2G6-associated neurodegeneration. 62 5
27378808 2016
19
Clinical heterogeneity of PLA2G6-related Parkinsonism: analysis of two Saudi families. 62 5
27268037 2016
20
Disruption of Golgi morphology and altered protein glycosylation in PLA2G6-associated neurodegeneration. 62 5
26668131 2016
21
Genetic Analysis of PLA2G6 in 22 Indian Families with Infantile Neuroaxonal Dystrophy, Atypical Late-Onset Neuroaxonal Dystrophy and Dystonia Parkinsonism Complex. 62 5
27196560 2016
22
Neuroimaging studies and whole exome sequencing of PLA2G6-associated neurodegeneration in a family with intrafamilial phenotypic heterogeneity. 62 5
25634434 2015
23
Follow-up study of 25 Chinese children with PLA2G6-associated neurodegeneration. 62 5
22934738 2013
24
Clinical and genetic delineation of neurodegeneration with brain iron accumulation. 62 57
18981035 2009
25
Infantile neuroaxonal dystrophy: what's most important for the diagnosis? 62 5
18359254 2008
26
PLA2G6-Associated Neurodegeneration 62 5
20301718 2008
27
Phenotypic spectrum of neurodegeneration associated with mutations in the PLA2G6 gene (PLAN). 62 57
18443314 2008
28
Disrupted membrane homeostasis and accumulation of ubiquitinated proteins in a mouse model of infantile neuroaxonal dystrophy caused by PLA2G6 mutations. 62 57
18202189 2008
29
Infantile neuroaxonal dystrophy and pantothenate-kinase-associated neurodegeneration: locus heterogeneity. 62 57
15365152 2004
30
Infantile neuroaxonal dystrophy: diagnosis by skin biopsy. 62 57
1659791 1991
31
Neuroaxonal dystrophy presenting with neonatal dysmorphic features, early onset of peripheral gangrene, and a rapidly lethal course. 62 57
3314508 1987
32
Diagnostic difficulties in infantile neuroaxonal dystrophy. A clinicopathological study of eight cases. 62 57
3683759 1987
33
Infantile neuroaxonal dystrophy: perinatal onset with symptoms of diencephalic syndrome. 62 57
2986047 1985
34
Neuroaxonal dystrophy in childhood. Report of two second cousins with Hallerworden-Spatz disease, and a case of Seitelberger's disease. 62 57
7158329 1982
35
Neuroaxonal dystrophy in young adults: a clinicopathological study of two unrelated cases. 62 57
7103414 1982
36
Infantile neuroaxonal dystrophy. 62 57
509195 1979
37
Juvenile neuroaxonal dystrophy: clinical, electrophysiological, and neuropathological features. 62 57
103487 1978
38
Neuroaxonal dystrophy (Seitelberger's disease) with late onset, protracted course and myoclonic epilepsy. 62 57
418153 1978
39
Infantile neuroaxonal dystrophy. 62 57
5829994 1965
40
INFANTILE NEUROAXONAL DYSTROPHY. 62 57
14237772 1965
41
Infantile neuroaxonal dystrophy. 62 57
14023529 1963
42
CNVs cause autosomal recessive genetic diseases with or without involvement of SNV/indels. 5
32576985 2020
43
Molecular diagnosis in recessive pediatric neurogenetic disease can help reduce disease recurrence in families. 5
32404165 2020
44
Atypical Childhood-onset Neuroaxonal Dystrophy in an Indian Girl. 5
31516627 2019
45
Impaired Transferrin Receptor Palmitoylation and Recycling in Neurodegeneration with Brain Iron Accumulation. 57
29395073 2018
46
Marked yield of re-evaluating phenotype and exome/target sequencing data in 33 individuals with intellectual disabilities. 5
29159939 2018
47
Neuropathology of genetic synucleinopathies with parkinsonism: Review of the literature. 5
29124790 2017
48
Novel mutations in PANK2 and PLA2G6 genes in patients with neurodegenerative disorders: two case reports. 5
28821231 2017
49
PLA2G6 mutations and Parkinsonism: Long-term follow-up of clinical features and neuropathology. 5
27709683 2016
50
Utility of whole exome sequencing for the early diagnosis of pediatric-onset cerebellar atrophy associated with developmental delay in an inbred population. 5
27146152 2016

Variations for Neurodegeneration with Brain Iron Accumulation 2a

ClinVar genetic disease variations for Neurodegeneration with Brain Iron Accumulation 2a:

5 (show top 50) (show all 364)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 PLA2G6 DEL Pathogenic
374373 GRCh37: 22:38565225-38565478
GRCh38:
2 PLA2G6 NM_003560.4(PLA2G6):c.1743-1G>C SNV Pathogenic
437466 rs1555979401 GRCh37: 22:38512219-38512219
GRCh38: 22:38116212-38116212
3 PLA2G6 NM_003560.4(PLA2G6):c.3G>T (p.Met1Ile) SNV Pathogenic
429031 rs764959600 GRCh37: 22:38565431-38565431
GRCh38: 22:38169424-38169424
4 PLA2G6 NM_003560.4(PLA2G6):c.1592-2A>C SNV Pathogenic
561085 rs1465629909 GRCh37: 22:38516918-38516918
GRCh38: 22:38120911-38120911
5 PLA2G6 NM_003560.4(PLA2G6):c.1931del (p.Phe644fs) DEL Pathogenic
570347 rs1569243565 GRCh37: 22:38511637-38511637
GRCh38: 22:38115630-38115630
6 PLA2G6 NC_000022.11:g.(?_38169198)_(38169446_?)del DEL Pathogenic
583663 GRCh37: 22:38565205-38565453
GRCh38: 22:38169198-38169446
7 PLA2G6 NM_003560.4(PLA2G6):c.929T>A (p.Val310Glu) SNV Pathogenic
6197 rs121908682 GRCh37: 22:38528986-38528986
GRCh38: 22:38132979-38132979
8 PLA2G6 NM_003560.4(PLA2G6):c.1262del (p.Val421fs) DEL Pathogenic
652932 rs1282370486 GRCh37: 22:38524362-38524362
GRCh38: 22:38128355-38128355
9 PLA2G6 NM_003560.4(PLA2G6):c.2035-2A>G SNV Pathogenic
692050 rs1602057157 GRCh37: 22:38509663-38509663
GRCh38: 22:38113656-38113656
10 PLA2G6 NM_003560.4(PLA2G6):c.2276+1G>A SNV Pathogenic
803689 rs1397030516 GRCh37: 22:38508510-38508510
GRCh38: 22:38112503-38112503
11 PLA2G6 NM_003560.4(PLA2G6):c.1880-1G>C SNV Pathogenic
813442 rs1025497590 GRCh37: 22:38511689-38511689
GRCh38: 22:38115682-38115682
12 PLA2G6 NM_003560.4(PLA2G6):c.1187-1G>A SNV Pathogenic
813443 rs1477656610 GRCh37: 22:38524438-38524438
GRCh38: 22:38128431-38128431
13 PLA2G6 NC_000022.11:g.(?_38132114)_(38135084_?)del DEL Pathogenic
832743 GRCh37: 22:38528121-38531091
GRCh38:
14 PLA2G6 GRCh37/hg19 22q13.1(chr22:38565225-38565434) CN LOSS Pathogenic
916003 GRCh37: 22:38565225-38565434
GRCh38:
15 PLA2G6 NM_003560.4(PLA2G6):c.2356G>A (p.Glu786Lys) SNV Pathogenic
998023 rs778705470 GRCh37: 22:38508233-38508233
GRCh38: 22:38112226-38112226
16 PLA2G6 NM_003560.4(PLA2G6):c.164G>A (p.Trp55Ter) SNV Pathogenic
803694 rs1177564212 GRCh37: 22:38565270-38565270
GRCh38: 22:38169263-38169263
17 PLA2G6 NC_000022.10:g.(?_38528818)_(38539315_?)dup DUP Pathogenic
1076982 GRCh37: 22:38528818-38539315
GRCh38:
18 PLA2G6 NM_003560.4(PLA2G6):c.533_536del (p.Gln178fs) DEL Pathogenic
986119 rs2089023572 GRCh37: 22:38539185-38539188
GRCh38: 22:38143178-38143181
19 PLA2G6 NC_000022.10:g.(?_38565205)_(38565433_?)del DEL Pathogenic
1453196 GRCh37: 22:38565205-38565433
GRCh38:
20 PLA2G6 NM_003560.4(PLA2G6):c.2032A>G (p.Lys678Glu) SNV Pathogenic
1686075 GRCh37: 22:38511536-38511536
GRCh38: 22:38115529-38115529
21 PLA2G6 NM_003560.4(PLA2G6):c.1969G>A (p.Ala657Thr) SNV Pathogenic
1686076 GRCh37: 22:38511599-38511599
GRCh38: 22:38115592-38115592
22 PLA2G6 NM_003560.4(PLA2G6):c.1474_1478del (p.Ile492fs) DEL Pathogenic
1686077 GRCh37: 22:38519215-38519219
GRCh38: 22:38123208-38123212
23 PLA2G6 NM_003560.4(PLA2G6):c.1069G>A (p.Ala357Thr) SNV Pathogenic
1686078 GRCh37: 22:38528846-38528846
GRCh38: 22:38132839-38132839
24 PLA2G6 NM_003560.4(PLA2G6):c.1442T>A (p.Leu481Gln) SNV Pathogenic
159731 rs587784330 GRCh37: 22:38519251-38519251
GRCh38: 22:38123244-38123244
25 PLA2G6 NM_003560.4(PLA2G6):c.437dup (p.Cys146fs) DUP Pathogenic
1686079 GRCh37: 22:38539283-38539284
GRCh38: 22:38143276-38143277
26 PLA2G6 NM_003560.4(PLA2G6):c.2128C>T (p.Arg710Cys) SNV Pathogenic
159759 rs587784347 GRCh37: 22:38509568-38509568
GRCh38: 22:38113561-38113561
27 PLA2G6 NM_003560.4(PLA2G6):c.2370_2371del (p.Tyr790_Glu791delinsTer) DEL Pathogenic
6201 rs587784353 GRCh37: 22:38508218-38508219
GRCh38: 22:38112211-38112212
28 PLA2G6 NM_003560.4(PLA2G6):c.1117G>A (p.Gly373Arg) SNV Pathogenic
159728 rs587784327 GRCh37: 22:38525530-38525530
GRCh38: 22:38129523-38129523
29 PLA2G6 NM_003560.4(PLA2G6):c.208C>T (p.Arg70Ter) SNV Pathogenic
265449 rs886039552 GRCh37: 22:38565226-38565226
GRCh38: 22:38169219-38169219
30 PLA2G6 NM_003560.4(PLA2G6):c.673C>T (p.His225Tyr) SNV Pathogenic
159775 rs587784359 GRCh37: 22:38536113-38536113
GRCh38: 22:38140106-38140106
31 PLA2G6 NM_003560.4(PLA2G6):c.991G>T (p.Asp331Tyr) SNV Pathogenic
30371 rs199935023 GRCh37: 22:38528924-38528924
GRCh38: 22:38132917-38132917
32 PLA2G6 NM_003560.4(PLA2G6):c.2341G>A (p.Ala781Thr) SNV Pathogenic
1459239 GRCh37: 22:38508248-38508248
GRCh38: 22:38112241-38112241
33 PLA2G6 NC_000022.10:g.(?_38528818)_(38536196_?)del DEL Pathogenic
1459347 GRCh37: 22:38528818-38536196
GRCh38:
34 PLA2G6 NG_007094.1:g.(45669_45717)_(52301_52349)del DEL Pathogenic
30369 GRCh37: 22:38530413-38537093
GRCh38: 22:38134406-38141086
35 PLA2G6 NM_003560.4(PLA2G6):c.1903C>T (p.Arg635Ter) SNV Pathogenic
Pathogenic
159749 rs587784339 GRCh37: 22:38511665-38511665
GRCh38: 22:38115658-38115658
36 PLA2G6 NM_003560.4(PLA2G6):c.2221C>T (p.Arg741Trp) SNV Pathogenic
265448 rs530348521 GRCh37: 22:38508566-38508566
GRCh38: 22:38112559-38112559
37 PLA2G6 NM_003560.4(PLA2G6):c.1039G>A (p.Gly347Arg) SNV Pathogenic
561083 rs1569263730 GRCh37: 22:38528876-38528876
GRCh38: 22:38132869-38132869
38 PLA2G6 NM_003560.4(PLA2G6):c.109C>T (p.Arg37Ter) SNV Pathogenic
30370 rs200075782 GRCh37: 22:38565325-38565325
GRCh38: 22:38169318-38169318
39 PLA2G6 NM_003560.4(PLA2G6):c.1547_1548dup (p.Gly517fs) DUP Pathogenic
523033 rs1555988204 GRCh37: 22:38519144-38519145
GRCh38: 22:38123137-38123138
40 PLA2G6 NM_003560.4(PLA2G6):c.1772G>A (p.Arg591Gln) SNV Pathogenic
803691 rs776713955 GRCh37: 22:38512189-38512189
GRCh38: 22:38116182-38116182
41 PLA2G6 NM_003560.4(PLA2G6):c.986G>A (p.Arg329His) SNV Pathogenic
159784 rs587784363 GRCh37: 22:38528929-38528929
GRCh38: 22:38132922-38132922
42 PLA2G6 NM_003560.4(PLA2G6):c.1771C>T (p.Arg591Trp) SNV Pathogenic
1298894 GRCh37: 22:38512190-38512190
GRCh38: 22:38116183-38116183
43 PLA2G6 NM_003560.4(PLA2G6):c.2370T>G (p.Tyr790Ter) SNV Pathogenic
Pathogenic
Pathogenic/Likely Pathogenic
6195 rs121908680 GRCh37: 22:38508219-38508219
GRCh38: 22:38112212-38112212
44 PLA2G6 NM_003560.4(PLA2G6):c.1077G>A (p.Ser359=) SNV Pathogenic
279875 rs368497893 GRCh37: 22:38528838-38528838
GRCh38: 22:38132831-38132831
45 PLA2G6 NM_003560.4(PLA2G6):c.755del (p.Asn252fs) DEL Pathogenic
159778 rs587784361 GRCh37: 22:38536031-38536031
GRCh38: 22:38140024-38140024
46 PLA2G6 NM_003560.4(PLA2G6):c.2222G>A (p.Arg741Gln) SNV Pathogenic
6203 rs121908686 GRCh37: 22:38508565-38508565
GRCh38: 22:38112558-38112558
47 PLA2G6 NM_003560.4(PLA2G6):c.1351del (p.Leu451fs) DEL Pathogenic
Likely Pathogenic
159730 rs587784329 GRCh37: 22:38522454-38522454
GRCh38: 22:38126447-38126447
48 PLA2G6 NM_003560.4(PLA2G6):c.1799G>A (p.Arg600Gln) SNV Pathogenic
159748 rs149712244 GRCh37: 22:38512162-38512162
GRCh38: 22:38116155-38116155
49 PLA2G6 NM_003560.4(PLA2G6):c.2070_2072del (p.Val691del) DEL Pathogenic
6198 rs587784343 GRCh37: 22:38509624-38509626
GRCh38: 22:38113617-38113619
50 overlap with 2 genes NM_003560.2(PLA2G6):c.-545_-46+1931delinsCGATCTC INDEL Pathogenic
584440 GRCh37: 22:38575740-38578170
GRCh38: 22:38179733-38182163

UniProtKB/Swiss-Prot genetic disease variations for Neurodegeneration with Brain Iron Accumulation 2a:

73
# Symbol AA change Variation ID SNP ID
1 PLA2G6 p.Val310Glu VAR_029371 rs121908682
2 PLA2G6 p.Asp484Gly VAR_070600
3 PLA2G6 p.Thr661Met VAR_070601 rs767689496
4 PLA2G6 p.Ala341Thr VAR_083527
5 PLA2G6 p.Gly517Cys VAR_083528
6 PLA2G6 p.Gly638Arg VAR_083529
7 PLA2G6 p.Arg741Trp VAR_083530

Expression for Neurodegeneration with Brain Iron Accumulation 2a

Search GEO for disease gene expression data for Neurodegeneration with Brain Iron Accumulation 2a.

Pathways for Neurodegeneration with Brain Iron Accumulation 2a

Pathways related to Neurodegeneration with Brain Iron Accumulation 2a according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.27 COASY FA2H PANK1 PANK2 PLA2G1B PLA2G6
2
Show member pathways
12.47 PNPLA8 PNPLA2 PLA2G6 PLA2G1B
3 12.04 PNPLA2 PLA2G1B PANK1 CP
4
Show member pathways
11.84 RPS27A FTL CP
5
Show member pathways
11.81 PNPLA8 PLA2G6 PLA2G1B
6
Show member pathways
11.5 PNPLA8 PLA2G6 PLA2G1B
7
Show member pathways
11.43 WDR45 PLA2G6 PANK2 FTL FA2H DCAF17
8 10.69 PNPLA2 PLA2G1B
9
Show member pathways
10.31 PANK2 PANK1 COASY

GO Terms for Neurodegeneration with Brain Iron Accumulation 2a

Biological processes related to Neurodegeneration with Brain Iron Accumulation 2a according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cellular iron ion homeostasis GO:0006879 9.85 FTL CP ATP13A2
2 lipid homeostasis GO:0055088 9.8 PNPLA8 PNPLA2 ATP13A2
3 phosphatidylcholine catabolic process GO:0034638 9.73 PNPLA8 PLA2G6
4 lipid metabolic process GO:0006629 9.73 FA2H NAGA PLA2G1B PLA2G6 PNPLA2 PNPLA8
5 cellular response to manganese ion GO:0071287 9.71 ATP13A2 APP
6 phosphatidylethanolamine catabolic process GO:0046338 9.46 PNPLA8 PLA2G6
7 lipid catabolic process GO:0016042 9.35 PNPLA8 PNPLA2 PLA2G6 PLA2G1B
8 coenzyme A biosynthetic process GO:0015937 9.1 PANK2 PANK1 COASY

Molecular functions related to Neurodegeneration with Brain Iron Accumulation 2a according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 catalytic activity GO:0003824 9.62 PNPLA8 PNPLA2 PLA2G6 COASY
2 phosphatidyl phospholipase B activity GO:0102545 9.56 PNPLA8 PLA2G6
3 calcium-independent phospholipase A2 activity GO:0047499 9.46 PNPLA8 PLA2G6
4 pantothenate kinase activity GO:0004594 9.26 PANK2 PANK1
5 phospholipase A2 activity GO:0004623 9.17 PNPLA8 PNPLA2 PLA2G6 PLA2G1B

Sources for Neurodegeneration with Brain Iron Accumulation 2a

2 CDC
6 CNVD
8 Cosmic
9 dbSNP
10 DGIdb
16 EFO
17 ExPASy
18 FMA
19 GARD
27 GO
28 GTR
29 HMDB
30 HPO
31 ICD10
32 ICD10 via Orphanet
33 ICD11
34 ICD9CM
35 IUPHAR
36 LifeMap
38 LOVD
40 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
52 NINDS
53 Novoseek
55 ODiseA
56 OMIM via Orphanet
57 OMIM® (Updated 08-Dec-2022)
61 PubChem
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 Tocris
71 UMLS
72 UMLS via Orphanet
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