SPG35
MCID: SPS153
MIFTS: 50

Spastic Paraplegia 35, Autosomal Recessive (SPG35)

Categories: Bone diseases, Ear diseases, Eye diseases, Gastrointestinal diseases, Genetic diseases, Mental diseases, Metabolic diseases, Muscle diseases, Nephrological diseases, Neuronal diseases, Rare diseases, Respiratory diseases, Skin diseases

Aliases & Classifications for Spastic Paraplegia 35, Autosomal Recessive

MalaCards integrated aliases for Spastic Paraplegia 35, Autosomal Recessive:

Name: Spastic Paraplegia 35, Autosomal Recessive 57 20 73 13
Fatty Acid Hydroxylase-Associated Neurodegeneration 57 12 25 20 43 58 73 71
Fahn 57 12 20 43 58 73
Spg35 57 12 20 58 73
Leukodystrophy, Dysmyelinating, and Spastic Paraparesis with or Without Dystonia 57 20 71
Spastic Paraplegia 35 43 29 6
Autosomal Recessive Spastic Paraplegia Type 35 12 58
Hereditary Spastic Paraplegia 35 12 15
Leukodystrophy, Dysmyelinating and Spastic Paraparesis with or Without Dystonia 12
Leukodystrophy Dysmyelinating and Spastic Paraparesis with or Without Dystonia 73
Fatty Acid Hydroxylase-Associated Neurodegeneration; Fahn 57
Dysmyelinating Leukodystrophy and Spastic Paraparesis 43
Paraplegia, Spastic, Autosomal Recessive, Type 35 39
Autosomal Recessive Spastic Paraplegia 35 12

Characteristics:

Orphanet epidemiological data:

58
autosomal recessive spastic paraplegia type 35
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Adolescent,Childhood; Age of death: adolescent,adult;
fatty acid hydroxylase-associated neurodegeneration
Prevalence: <1/1000000 (Worldwide); Age of onset: Adolescent,Childhood;

OMIM®:

57 (Updated 05-Mar-2021)
Inheritance:
autosomal recessive

Miscellaneous:
progressive disorder
onset between 3 and 11 years of age
most patients become wheelchair-bound in adolescence or as young adults


HPO:

31
spastic paraplegia 35, autosomal recessive:
Inheritance autosomal recessive inheritance
Onset and clinical course progressive


Classifications:

Orphanet: 58  
Rare neurological diseases
Rare eye diseases
Inborn errors of metabolism


Summaries for Spastic Paraplegia 35, Autosomal Recessive

MedlinePlus Genetics : 43 Fatty acid hydroxylase-associated neurodegeneration (FAHN) is a progressive disorder of the nervous system (neurodegeneration) characterized by problems with movement and vision that begin during childhood or adolescence.Changes in the way a person walks (gait) and frequent falls are usually the first noticeable signs of FAHN. Affected individuals gradually develop extreme muscle stiffness (spasticity) and exaggerated reflexes. They typically have involuntary muscle cramping (dystonia), problems with coordination and balance (ataxia), or both. The movement problems worsen over time, and some people with this condition eventually require wheelchair assistance.People with FAHN often develop vision problems, which occur due to deterioration (atrophy) of the nerves that carry information from the eyes to the brain (the optic nerves) and difficulties with the muscles that control eye movement. Affected individuals may have a loss of sharp vision (reduced visual acuity), decreased field of vision, impaired color perception, eyes that do not look in the same direction (strabismus), rapid involuntary eye movements (nystagmus), or difficulty moving the eyes intentionally (supranuclear gaze palsy).Speech impairment (dysarthria) also occurs in FAHN, and severely affected individuals may lose the ability to speak. People with this disorder may also have difficulty chewing or swallowing (dysphagia). In severe cases, they may develop malnutrition and require a feeding tube. The swallowing difficulties can lead to a bacterial lung infection called aspiration pneumonia, which can be life-threatening. As the disorder progresses, some affected individuals experience seizures and a decline in intellectual function.Magnetic resonance imaging (MRI) of the brain in people with FAHN shows signs of iron accumulation, especially in an area of the brain called the globus pallidus, which is involved in regulating movement. Similar patterns of iron accumulation are seen in certain other neurological disorders such as infantile neuroaxonal dystrophy and pantothenate kinase-associated neurodegeneration. All these conditions belong to a class of disorders called neurodegeneration with brain iron accumulation (NBIA).

MalaCards based summary : Spastic Paraplegia 35, Autosomal Recessive, also known as fatty acid hydroxylase-associated neurodegeneration, is related to spastic paraparesis and axonal neuropathy, and has symptoms including seizures, ataxia and urgency of micturition. An important gene associated with Spastic Paraplegia 35, Autosomal Recessive is FA2H (Fatty Acid 2-Hydroxylase), and among its related pathways/superpathways is Pantothenate and CoA biosynthesis. Affiliated tissues include brain, eye and globus pallidus, and related phenotypes are mental deterioration and spastic paraplegia

Disease Ontology : 12 A hereditary spastic paraplegia that has material basis in mutation in the FA2H gene on chromosome 16q23.1.

GARD : 20 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 329308DefinitionFatty acid hydroxylase-associated neurodegeneration (FAHN) is a very rare, autosomal recessive form of neurodegeneration with brain iron accumulation (NBIA) characterized by childhood-onset focal dystonia, progressive spastic paraplegia that progresses to tetra paresis, ataxia, dysarthria, intellectual decline, and oculomotor disturbances (optic atrophy), accompanied by iron deposition in the globus pallidus.Visit the Orphanet disease page for more resources.

OMIM® : 57 Autosomal recessive spastic paraplegia-35 is a complicated form of SPG characterized by childhood onset of gait difficulties due to progressive spastic paraparesis, dysarthria, and mild cognitive decline associated with leukodystrophy on brain imaging. Other variable neurologic features, such as dystonia, optic atrophy, and seizures may also occur (summary by Dick et al., 2010). In addition, some patients with mutations in the FA2H gene have radiographic evidence of neurodegeneration with brain iron accumulation (NBIA), thus expanding the phenotype. Kruer et al. (2010) referred to this phenotypic spectrum of disorders as fatty acid hydrolase-associated neurodegeneration (FAHN). For a discussion of genetic heterogeneity of autosomal recessive spastic paraplegia, see SPG5A (270800). (612319) (Updated 05-Mar-2021)

UniProtKB/Swiss-Prot : 73 Spastic paraplegia 35, autosomal recessive: A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. SPG35 is a complicated form characterized by childhood onset of gait difficulties. It has a rapid progression and many patients become wheelchair-bound as young adults. Patients manifest cognitive decline associated with leukodystrophy. Other variable neurologic features, such as dystonia, optic atrophy, and seizures may also occur.

GeneReviews: NBK56080

Related Diseases for Spastic Paraplegia 35, Autosomal Recessive

Diseases in the Spastic Paraplegia 3a family:

Spastic Paraplegia 3, Autosomal Dominant Spastic Paraplegia 4, Autosomal Dominant
Spastic Paraplegia 17, Autosomal Dominant Spastic Paraplegia 15, Autosomal Recessive
Spastic Paraplegia 23, Autosomal Recessive Spastic Paraplegia 5a, Autosomal Recessive
Spastic Paraplegia 20, Autosomal Recessive Spastic Paraplegia 6, Autosomal Dominant
Spastic Paraplegia 9a, Autosomal Dominant Spastic Paraplegia 8, Autosomal Dominant
Spastic Paraplegia 10, Autosomal Dominant Spastic Paraplegia 11, Autosomal Recessive
Spastic Paraplegia 12, Autosomal Dominant Spastic Paraplegia 14, Autosomal Recessive
Spastic Paraplegia 13, Autosomal Dominant Spastic Paraplegia 19, Autosomal Dominant
Spastic Paraplegia 7, Autosomal Recessive Spastic Paraplegia 24, Autosomal Recessive
Spastic Paraplegia 25, Autosomal Recessive Spastic Paraplegia 27, Autosomal Recessive
Spastic Paraplegia 26, Autosomal Recessive Spastic Paraplegia 28, Autosomal Recessive
Spastic Paraplegia 29, Autosomal Dominant Spastic Paraplegia 33, Autosomal Dominant
Spastic Paraplegia 31, Autosomal Dominant Spastic Paraplegia 30, Autosomal Dominant
Spastic Paraplegia 18, Autosomal Recessive Spastic Paraplegia 32, Autosomal Recessive
Spastic Paraplegia 37, Autosomal Dominant Spastic Paraplegia 39, Autosomal Recessive
Spastic Paraplegia 35, Autosomal Recessive Spastic Paraplegia 38, Autosomal Dominant
Spastic Paraplegia 42, Autosomal Dominant Spastic Paraplegia 50, Autosomal Recessive
Spastic Paraplegia 36, Autosomal Dominant Spastic Paraplegia 45, Autosomal Recessive
Spastic Paraplegia 44, Autosomal Recessive Spastic Paraplegia 41, Autosomal Dominant
Spastic Paraplegia 48, Autosomal Recessive Spastic Paraplegia 51, Autosomal Recessive
Spastic Paraplegia 47, Autosomal Recessive Spastic Paraplegia 52, Autosomal Recessive
Spastic Paraplegia 46, Autosomal Recessive Spastic Paraplegia 53, Autosomal Recessive
Spastic Paraplegia 56, Autosomal Recessive Spastic Paraplegia 49, Autosomal Recessive
Spastic Paraplegia 54, Autosomal Recessive Spastic Paraplegia 55, Autosomal Recessive
Spastic Paraplegia 43, Autosomal Recessive Spastic Paraplegia 79, Autosomal Recessive
Spastic Paraplegia 72, Autosomal Recessive Spastic Paraplegia 57, Autosomal Recessive
Spastic Paraplegia 62, Autosomal Recessive Spastic Paraplegia 64, Autosomal Recessive
Spastic Paraplegia 61, Autosomal Recessive Spastic Paraplegia 63, Autosomal Recessive
Spastic Paraplegia 73, Autosomal Dominant Spastic Paraplegia 74, Autosomal Recessive
Spastic Paraplegia 9b, Autosomal Recessive Spastic Paraplegia 75, Autosomal Recessive
Spastic Paraplegia 76, Autosomal Recessive Spastic Paraplegia 77, Autosomal Recessive
Spastic Paraplegia 78, Autosomal Recessive Spastic Paraplegia 80, Autosomal Dominant
Spastic Paraplegia 81, Autosomal Recessive Spastic Paraplegia 82, Autosomal Recessive
Spastic Paraplegia 83, Autosomal Recessive Hereditary Spastic Paraplegia 23
Hereditary Spastic Paraplegia 30 Hereditary Spastic Paraplegia 51
Hereditary Spastic Paraplegia 72 Hereditary Spastic Paraplegia
Spastic Paraplegia 4 Spastic Paraplegia 8
Spastic Paraplegia 11 Spastic Paraplegia 10
Spastic Paraplegia 12 Spastic Paraplegia 13
Spastic Paraplegia 14 Spastic Paraplegia 15
Spastic Paraplegia 16 Spastic Paraplegia 17
Spastic Paraplegia 18 Spastic Paraplegia 19
Spastic Paraplegia 24 Spastic Paraplegia 25
Spastic Paraplegia 26 Spastic Paraplegia 29
Spastic Paraplegia 3 Spastic Paraplegia 32
Spastic Paraplegia 39 Spastic Paraplegia 47
Spastic Paraplegia 5a Spastic Paraplegia 5b
Spastic Paraplegia 6 Spastic Paraplegia 9
Spastic Paraplegia Type 49 Autosomal Recessive Spastic Paraplegia Type 60
Autosomal Recessive Spastic Paraplegia Type 59 Autosomal Recessive Spastic Paraplegia Type 69
Autosomal Recessive Spastic Paraplegia Type 70 Autosomal Recessive Spastic Paraplegia Type 71
Autosomal Recessive Spastic Paraplegia Type 66 Autosomal Recessive Spastic Paraplegia Type 67
Autosomal Dominant Spastic Paraplegia Type 9b

Diseases related to Spastic Paraplegia 35, Autosomal Recessive via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 113)
# Related Disease Score Top Affiliating Genes
1 spastic paraparesis 30.0 SPG7 SPG11 FA2H
2 axonal neuropathy 29.8 ZFYVE26 SPG11 C19orf12
3 spastic paraplegia 7, autosomal recessive 29.8 SPG7 SPG11 PNPLA6
4 spastic paraplegia 11, autosomal recessive 29.8 ZFYVE26 SPG7 SPG21 SPG11 AP5Z1
5 mast syndrome 29.7 SPG21 SPG11
6 movement disease 29.4 WDR45 PLA2G6 PANK2 C19orf12 ATP13A2
7 neurodegeneration with brain iron accumulation 29.0 WDR45 SPG11 PLA2G6 PANK2 FA2H DCAF17
8 dystonia 28.9 WDR45 PLA2G6 PANK2 FA2H DCAF17 COASY
9 spastic paraplegia 54, autosomal recessive 28.6 SPG7 SPG21 SPG11 REEP1 PNPLA6 FA2H
10 spastic paraplegia 48, autosomal recessive 28.3 ZFYVE26 WASHC5 SPG7 SPG21 SPG11 REEP1
11 spastic paraplegia 15, autosomal recessive 27.8 ZFYVE26 WASHC5 SPG7 SPG21 SPG11 REEP1
12 paraplegia 27.4 ZFYVE26 WASHC5 SPG7 SPG21 SPG11 REEP1
13 hereditary spastic paraplegia 27.1 ZFYVE26 WASHC5 SPG7 SPG21 SPG11 REEP1
14 mitochondrial membrane protein-associated neurodegeneration 11.4
15 essential tremor 10.2
16 tremor 10.2
17 spastic paraplegia 76, autosomal recessive 10.2 SPG11 ATP13A2
18 spastic paraplegia 14, autosomal recessive 10.2 SPG7 SPG21 SPG11
19 spastic paraplegia 64, autosomal recessive 10.2 SPG7 SPG21 SPG11
20 congenital disorder of glycosylation, type ip 10.2 PANK2 C19orf12
21 3-methylglutaconic aciduria, type iii 10.1
22 spastic paraplegia 45, autosomal recessive 10.1 SPG21 SPG11 DDHD2
23 charcot-marie-tooth disease, axonal, type 2r 10.1 ZFYVE26 SPG21
24 alcohol-related neurodevelopmental disorder 10.1 WDR45 C19orf12
25 behr syndrome 10.1 SPG7 C19orf12
26 spasticity 10.1
27 spastic paraplegia 53, autosomal recessive 10.1 WASHC5 AP5Z1
28 early-onset parkinson's disease 10.1 PLA2G6 C19orf12 ATP13A2
29 amyotrophic lateral sclerosis type 5 10.1 ZFYVE26 SPG11 AP5Z1
30 choreatic disease 10.0 PANK2 C19orf12 ATP13A2
31 spastic paraplegia 57, autosomal recessive 10.0 SPG11 REEP1
32 spastic paraplegia, optic atrophy, and neuropathy 10.0 WASHC5 AP5Z1
33 amyotrophic lateral sclerosis 1 10.0
34 ataxia and polyneuropathy, adult-onset 10.0
35 alacrima, achalasia, and mental retardation syndrome 10.0
36 leukodystrophy 10.0
37 lateral sclerosis 10.0
38 spastic paraplegia 15 10.0
39 spastic paraplegia 5a 10.0 CYP7B1 C19orf12
40 spastic paraplegia 55, autosomal recessive 10.0 ZFYVE26 SPG7 SPG21 SPG11
41 spastic paraplegia 16, x-linked 10.0 WASHC5 SPG7 SPG21 SPG11
42 spastic paraplegia 29, autosomal dominant 10.0 ZFYVE26 WASHC5 SPG21
43 spastic paraplegia 32, autosomal recessive 10.0 WASHC5 SPG7 SPG21 SPG11
44 spastic paraplegia 52, autosomal recessive 10.0 ZFYVE26 SPG21 SPG11 AP5Z1
45 spastic paraplegia 19, autosomal dominant 10.0 ZFYVE26 WASHC5 SPG21
46 charcot-marie-tooth disease, axonal, type 2t 10.0 ZFYVE26 SPG21
47 spastic paraplegia 3, autosomal dominant 9.9 SPG7 SPG11 REEP1
48 polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataract 9.9 PNPLA6 DDHD2
49 neuropathy, hereditary sensory, type iic 9.9 SPG21 SPG11 REEP1 FA2H
50 oromandibular dystonia 9.9 PLA2G6 PANK2 FA2H C19orf12 ATP13A2

Graphical network of the top 20 diseases related to Spastic Paraplegia 35, Autosomal Recessive:



Diseases related to Spastic Paraplegia 35, Autosomal Recessive

Symptoms & Phenotypes for Spastic Paraplegia 35, Autosomal Recessive

Human phenotypes related to Spastic Paraplegia 35, Autosomal Recessive:

58 31 (show top 50) (show all 74)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 mental deterioration 58 31 frequent (33%) Frequent (79-30%),Very frequent (99-80%) HP:0001268
2 spastic paraplegia 58 31 hallmark (90%) Very frequent (99-80%) HP:0001258
3 babinski sign 58 31 hallmark (90%) Very frequent (99-80%) HP:0003487
4 progressive spastic paraplegia 58 31 hallmark (90%) Very frequent (99-80%) HP:0007020
5 progressive gait ataxia 58 31 hallmark (90%) Very frequent (99-80%) HP:0007240
6 difficulty walking 58 31 hallmark (90%) Very frequent (99-80%) HP:0002355
7 foot dorsiflexor weakness 58 31 hallmark (90%) Very frequent (99-80%) HP:0009027
8 falls 58 31 hallmark (90%) Very frequent (99-80%) HP:0002527
9 intellectual disability 58 31 frequent (33%) Frequent (79-30%) HP:0001249
10 dysarthria 58 31 frequent (33%) Frequent (79-30%),Frequent (79-30%) HP:0001260
11 optic atrophy 58 31 very rare (1%) Very rare (<4-1%),Frequent (79-30%) HP:0000648
12 dysmetria 58 31 frequent (33%) Frequent (79-30%) HP:0001310
13 dysdiadochokinesis 58 31 frequent (33%) Frequent (79-30%) HP:0002075
14 generalized dystonia 58 31 frequent (33%) Frequent (79-30%),Frequent (79-30%) HP:0007325
15 hypoplasia of the corpus callosum 58 31 frequent (33%) Frequent (79-30%),Frequent (79-30%) HP:0002079
16 cerebellar atrophy 58 31 frequent (33%) Frequent (79-30%),Frequent (79-30%) HP:0001272
17 progressive spastic quadriplegia 58 31 frequent (33%) Frequent (79-30%) HP:0002478
18 spastic tetraparesis 58 31 frequent (33%) Frequent (79-30%) HP:0001285
19 oculomotor apraxia 58 31 frequent (33%) Frequent (79-30%) HP:0000657
20 loss of ability to walk 58 31 frequent (33%) Frequent (79-30%) HP:0006957
21 visual field defect 58 31 frequent (33%) Frequent (79-30%) HP:0001123
22 anarthria 58 31 frequent (33%) Frequent (79-30%) HP:0002425
23 cerebellar vermis atrophy 58 31 frequent (33%) Frequent (79-30%) HP:0006855
24 frequent falls 58 31 frequent (33%) Frequent (79-30%) HP:0002359
25 ankle clonus 58 31 occasional (7.5%) Frequent (79-30%) HP:0011448
26 atrophy/degeneration affecting the brainstem 58 31 frequent (33%) Frequent (79-30%) HP:0007366
27 horizontal nystagmus 58 31 frequent (33%) Frequent (79-30%) HP:0000666
28 atrophy of the spinal cord 58 31 frequent (33%) Frequent (79-30%) HP:0006827
29 corpus callosum atrophy 58 31 frequent (33%) Frequent (79-30%) HP:0007371
30 progressive extrapyramidal movement disorder 58 31 frequent (33%) Frequent (79-30%) HP:0007153
31 supranuclear gaze palsy 58 31 frequent (33%) Frequent (79-30%) HP:0000605
32 slow decrease in visual acuity 58 31 frequent (33%) Frequent (79-30%) HP:0007924
33 motor aphasia 58 31 frequent (33%) Frequent (79-30%) HP:0002427
34 progressive spastic paraparesis 58 31 frequent (33%) Frequent (79-30%) HP:0007199
35 lower limb hypertonia 58 31 frequent (33%) Frequent (79-30%) HP:0006895
36 color vision test abnormality 58 31 frequent (33%) Frequent (79-30%) HP:0030584
37 bilateral tonic-clonic seizure 31 frequent (33%) HP:0002069
38 kyphosis 58 31 occasional (7.5%) Occasional (29-5%) HP:0002808
39 bowel incontinence 58 31 occasional (7.5%) Occasional (29-5%) HP:0002607
40 strabismus 58 31 occasional (7.5%) Occasional (29-5%) HP:0000486
41 mask-like facies 58 31 occasional (7.5%) Occasional (29-5%) HP:0000298
42 cerebral cortical atrophy 58 31 occasional (7.5%) Occasional (29-5%) HP:0002120
43 urinary incontinence 58 31 occasional (7.5%) Occasional (29-5%) HP:0000020
44 pollakisuria 58 31 occasional (7.5%) Occasional (29-5%) HP:0100515
45 positional foot deformity 58 31 occasional (7.5%) Occasional (29-5%) HP:0005656
46 neck muscle weakness 58 31 occasional (7.5%) Occasional (29-5%) HP:0000467
47 pontocerebellar atrophy 58 31 occasional (7.5%) Occasional (29-5%) HP:0006879
48 enuresis nocturna 58 31 occasional (7.5%) Occasional (29-5%) HP:0010677
49 peripheral demyelination 58 31 occasional (7.5%) Occasional (29-5%) HP:0011096
50 iron accumulation in globus pallidus 58 31 occasional (7.5%) Occasional (29-5%) HP:0012677

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Mar-2021)
Neurologic Central Nervous System:
seizures
hyperreflexia
ataxia
dysarthria
dysmetria
more
Genitourinary Bladder:
urinary urgency
urinary incontinence (variable)

Head And Neck Eyes:
nystagmus
optic atrophy
strabismus
external ophthalmoplegia (less common)

Clinical features from OMIM®:

612319 (Updated 05-Mar-2021)

UMLS symptoms related to Spastic Paraplegia 35, Autosomal Recessive:


seizures, ataxia, urgency of micturition

MGI Mouse Phenotypes related to Spastic Paraplegia 35, Autosomal Recessive:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 10 AP5Z1 ATP13A2 COASY DDHD2 FA2H PANK2
2 cellular MP:0005384 9.73 AP5Z1 ATP13A2 COASY DCAF17 PANK2 PLA2G6
3 nervous system MP:0003631 9.47 AP5Z1 ATP13A2 COASY DDHD2 FA2H PANK2

Drugs & Therapeutics for Spastic Paraplegia 35, Autosomal Recessive

Search Clinical Trials , NIH Clinical Center for Spastic Paraplegia 35, Autosomal Recessive

Genetic Tests for Spastic Paraplegia 35, Autosomal Recessive

Genetic tests related to Spastic Paraplegia 35, Autosomal Recessive:

# Genetic test Affiliating Genes
1 Spastic Paraplegia 35 29 FA2H

Anatomical Context for Spastic Paraplegia 35, Autosomal Recessive

MalaCards organs/tissues related to Spastic Paraplegia 35, Autosomal Recessive:

40
Brain, Eye, Globus Pallidus, Spinal Cord

Publications for Spastic Paraplegia 35, Autosomal Recessive

Articles related to Spastic Paraplegia 35, Autosomal Recessive:

(show all 29)
# Title Authors PMID Year
1
Exome sequencing and SNP analysis detect novel compound heterozygosity in fatty acid hydroxylase-associated neurodegeneration. 25 6 57 61
22146942 2012
2
Phenotypic variability of a likely FA2H founder mutation in a family with complicated hereditary spastic paraplegia. 25 57 6
23745665 2014
3
Defective FA2H leads to a novel form of neurodegeneration with brain iron accumulation (NBIA). 57 6 25
20853438 2010
4
Mutation of FA2H underlies a complicated form of hereditary spastic paraplegia (SPG35). 25 6 57
20104589 2010
5
Mutations in the fatty acid 2-hydroxylase gene are associated with leukodystrophy with spastic paraparesis and dystonia. 25 6 57
19068277 2008
6
A novel locus for an autosomal recessive hereditary spastic paraplegia (SPG35) maps to 16q21-q23. 57 25
18463364 2008
7
Impaired Transferrin Receptor Palmitoylation and Recycling in Neurodegeneration with Brain Iron Accumulation. 57
29395073 2018
8
SPG35 contributes to the second common subtype of AR-HSP in China: frequency analysis and functional characterization of FA2H gene mutations. 57
24359114 2015
9
Exome sequencing reveals two FA2H mutations in a family with a complicated form of Hereditary Spastic Paraplegia and psychiatric impairments. 25
28017243 2017
10
Uniparental disomy of chromosome 16 unmasks recessive mutations of FA2H/SPG35 in 4 families. 25
27316240 2016
11
Mutations in FA2H in three Arab families with a clinical spectrum of neurodegeneration and hereditary spastic paraparesis. 25
25496456 2015
12
Case definition and classification of leukodystrophies and leukoencephalopathies. 25
25649058 2015
13
Atypical adult onset complicated spastic paraparesis with thin corpus callosum in two patients carrying a novel FA2H mutation. 25
22925154 2012
14
Deferiprone reduces hemosiderin deposits in the brain of a patient with superficial siderosis. 25
21051507 2011
15
Fatty acid 2-hydroxylase mediates diffusional mobility of Raft-associated lipids, GLUT4 level, and lipogenesis in 3T3-L1 adipocytes. 25
20519515 2010
16
Riluzole in cerebellar ataxia: a randomized, double-blind, placebo-controlled pilot trial. 25
20211908 2010
17
Fatty acid 2-hydroxylase regulates cAMP-induced cell cycle exit in D6P2T schwannoma cells. 25
19171550 2009
18
Selective iron chelation in Friedreich ataxia: biologic and clinical implications. 25
17379741 2007
19
A mammalian fatty acid hydroxylase responsible for the formation of alpha-hydroxylated galactosylceramide in myelin. 25
15658937 2005
20
The human FA2H gene encodes a fatty acid 2-hydroxylase. 25
15337768 2004
21
Stereotactic pallidotomy in a child with Hallervorden-Spatz disease. Case report. 25
10067928 1999
22
Decreased turnover of the CNS myelin protein Opalin in a mouse model of hereditary spastic paraplegia 35. 61
33215680 2021
23
Novel biallelic FA2H mutations in a Japanese boy with fatty acid hydroxylase-associated neurodegeneration. 61
31837835 2020
24
FAHN/SPG35: a narrow phenotypic spectrum across disease classifications. 61
31135052 2019
25
Identification of progesterone receptor membrane component-1 as an interaction partner and possible regulator of fatty acid 2-hydroxylase. 61
29438993 2018
26
Neurodegeneration with brain iron accumulation. 61
29325618 2018
27
A diagnostic approach for neurodegeneration with brain iron accumulation: clinical features, genetics and brain imaging. 61
27487380 2016
28
Syndromes of neurodegeneration with brain iron accumulation. 61
22704258 2012
29
Fatty Acid Hydroxylase-Associated Neurodegeneration 61
21735565 2011

Variations for Spastic Paraplegia 35, Autosomal Recessive

ClinVar genetic disease variations for Spastic Paraplegia 35, Autosomal Recessive:

6 (show top 50) (show all 89)
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 FA2H NM_024306.5(FA2H):c.159_176del (p.Arg53_Ile58del) Deletion Pathogenic 30871 rs759947457 16:74808478-74808495 16:74774580-74774597
2 FA2H NM_024306.5(FA2H):c.460C>T (p.Arg154Cys) SNV Pathogenic 30872 rs387907040 16:74761188-74761188 16:74727290-74727290
3 FA2H NM_024306.5(FA2H):c.510_511del (p.Tyr170_Ser171delinsTer) Deletion Pathogenic 30873 rs587776891 16:74760225-74760226 16:74726327-74726328
4 FA2H NM_024306.5(FA2H):c.707T>C (p.Phe236Ser) SNV Pathogenic 31624 rs387907172 16:74752965-74752965 16:74719067-74719067
5 FA2H NG_017070.1:g.(39810_52446)_(66877_?)del Deletion Pathogenic 31625 16:74746853-74773920 16:74712955-74740022
6 FA2H NM_024306.5(FA2H):c.786+1G>A SNV Pathogenic 1043 rs1567633766 16:74752885-74752885 16:74718987-74718987
7 FA2H NM_024306.5(FA2H):c.103G>T (p.Asp35Tyr) SNV Pathogenic 1044 rs121918217 16:74808551-74808551 16:74774653-74774653
8 FA2H NM_024306.5(FA2H):c.968C>T (p.Pro323Leu) SNV Pathogenic 807416 rs774131656 16:74750316-74750316 16:74716418-74716418
9 FA2H NM_024306.5(FA2H):c.102C>G (p.Tyr34Ter) SNV Pathogenic 488512 rs957683798 16:74808552-74808552 16:74774654-74774654
10 FA2H NM_024306.5(FA2H):c.340_363+8del Deletion Pathogenic 803271 rs1597556143 16:74773913-74773944 16:74740015-74740046
11 FA2H NM_024306.5(FA2H):c.150_159GCGGGCCAGG[1] (p.Ala54fs) Microsatellite Likely pathogenic 803272 rs794729214 16:74808485-74808494 16:74774587-74774596
12 FA2H NM_024306.5(FA2H):c.1119A>T (p.Ter373Cys) SNV Likely pathogenic 807415 rs758814013 16:74748088-74748088 16:74714190-74714190
13 FA2H NM_024306.5(FA2H):c.934G>T (p.Asp312Tyr) SNV Likely pathogenic 617530 rs1274600570 16:74750350-74750350 16:74716452-74716452
14 FA2H NM_024306.5(FA2H):c.910G>A (p.Gly304Ser) SNV Likely pathogenic 617531 rs1567632441 16:74750374-74750374 16:74716476-74716476
15 FA2H NM_024306.5(FA2H):c.133G>T (p.Gly45Trp) SNV Likely pathogenic 584457 rs1247665387 16:74808521-74808521 16:74774623-74774623
16 FA2H NM_024306.5(FA2H):c.806G>A (p.Arg269His) SNV Likely pathogenic 948467 16:74750478-74750478 16:74716580-74716580
17 FA2H NM_024306.5(FA2H):c.117C>A (p.Phe39Leu) SNV Likely pathogenic 242579 rs794729215 16:74808537-74808537 16:74774639-74774639
18 FA2H NM_024306.5(FA2H):c.517C>T (p.Pro173Ser) SNV Likely pathogenic 216927 rs863224870 16:74760219-74760219 16:74726321-74726321
19 FA2H NM_024306.5(FA2H):c.703C>T (p.Arg235Cys) SNV Conflicting interpretations of pathogenicity 30870 rs387907039 16:74752969-74752969 16:74719071-74719071
20 FA2H NM_024306.5(FA2H):c.*887T>A SNV Uncertain significance 320469 rs886052285 16:74747201-74747201 16:74713303-74713303
21 FA2H NM_024306.4(FA2H):c.-74C>T SNV Uncertain significance 320502 rs886052292 16:74808727-74808727 16:74774829-74774829
22 FA2H NM_024306.5(FA2H):c.*652C>T SNV Uncertain significance 320475 rs886052287 16:74747436-74747436 16:74713538-74713538
23 FA2H NM_024306.5(FA2H):c.*62G>A SNV Uncertain significance 320489 rs528642838 16:74748026-74748026 16:74714128-74714128
24 FA2H NM_024306.5(FA2H):c.1030C>G (p.Gln344Glu) SNV Uncertain significance 320494 rs748697810 16:74750254-74750254 16:74716356-74716356
25 FA2H NM_024306.5(FA2H):c.570C>A (p.Thr190=) SNV Uncertain significance 320496 rs138892784 16:74760166-74760166 16:74726268-74726268
26 FA2H NM_024306.5(FA2H):c.232G>A (p.Glu78Lys) SNV Uncertain significance 320501 rs527421775 16:74808422-74808422 16:74774524-74774524
27 FA2H NM_024306.5(FA2H):c.429G>A (p.Glu143=) SNV Uncertain significance 320499 rs886052290 16:74761219-74761219 16:74727321-74727321
28 FA2H NM_024306.5(FA2H):c.*646T>G SNV Uncertain significance 320476 rs886052288 16:74747442-74747442 16:74713544-74713544
29 FA2H NM_024306.5(FA2H):c.*772C>A SNV Uncertain significance 320473 rs886052286 16:74747316-74747316 16:74713418-74713418
30 FA2H NM_024306.5(FA2H):c.*506C>G SNV Uncertain significance 320479 rs774188909 16:74747582-74747582 16:74713684-74713684
31 FA2H NM_024306.5(FA2H):c.385C>T (p.Pro129Ser) SNV Uncertain significance 320500 rs886052291 16:74761263-74761263 16:74727365-74727365
32 FA2H NM_024306.5(FA2H):c.540G>T (p.Val180=) SNV Uncertain significance 320497 rs150423523 16:74760196-74760196 16:74726298-74726298
33 FA2H NM_024306.5(FA2H):c.600G>A (p.Thr200=) SNV Uncertain significance 697866 rs774718977 16:74760136-74760136 16:74726238-74726238
34 FA2H NM_024306.5(FA2H):c.338G>A (p.Arg113Gln) SNV Uncertain significance 241461 rs147632811 16:74773946-74773946 16:74740048-74740048
35 FA2H NM_024306.5(FA2H):c.337C>T (p.Arg113Trp) SNV Uncertain significance 381515 rs141276237 16:74773947-74773947 16:74740049-74740049
36 FA2H NM_024306.5(FA2H):c.*1074G>A SNV Uncertain significance 885528 16:74747014-74747014 16:74713116-74713116
37 FA2H NM_024306.5(FA2H):c.*185G>T SNV Uncertain significance 885598 16:74747903-74747903 16:74714005-74714005
38 FA2H NM_024306.5(FA2H):c.*165G>A SNV Uncertain significance 885599 16:74747923-74747923 16:74714025-74714025
39 FA2H NM_024306.5(FA2H):c.*59C>G SNV Uncertain significance 885600 16:74748029-74748029 16:74714131-74714131
40 FA2H NM_024306.5(FA2H):c.1112C>T (p.Thr371Met) SNV Uncertain significance 444377 rs141854925 16:74748095-74748095 16:74714197-74714197
41 FA2H NM_024306.5(FA2H):c.271-8C>A SNV Uncertain significance 696416 rs199610820 16:74774021-74774021 16:74740123-74740123
42 FA2H NM_024306.5(FA2H):c.266A>T (p.Gln89Leu) SNV Uncertain significance 885662 16:74808388-74808388 16:74774490-74774490
43 FA2H NM_024306.5(FA2H):c.94C>G (p.Arg32Gly) SNV Uncertain significance 406878 rs978032580 16:74808560-74808560 16:74774662-74774662
44 FA2H NM_024306.5(FA2H):c.*885G>T SNV Uncertain significance 886553 16:74747203-74747203 16:74713305-74713305
45 FA2H NM_024306.5(FA2H):c.1101C>G (p.Pro367=) SNV Uncertain significance 886623 16:74748106-74748106 16:74714208-74714208
46 FA2H NM_024306.5(FA2H):c.*505G>T SNV Uncertain significance 887808 16:74747583-74747583 16:74713685-74713685
47 FA2H NM_024306.5(FA2H):c.798C>T (p.Asp266=) SNV Uncertain significance 700054 rs771402018 16:74750486-74750486 16:74716588-74716588
48 FA2H NM_024306.5(FA2H):c.786+7G>A SNV Uncertain significance 700437 rs368669121 16:74752879-74752879 16:74718981-74718981
49 FA2H NM_024306.5(FA2H):c.786+6C>T SNV Uncertain significance 887871 16:74752880-74752880 16:74718982-74718982
50 FA2H NM_024306.5(FA2H):c.*391C>T SNV Uncertain significance 320482 rs563533561 16:74747697-74747697 16:74713799-74713799

UniProtKB/Swiss-Prot genetic disease variations for Spastic Paraplegia 35, Autosomal Recessive:

73
# Symbol AA change Variation ID SNP ID
1 FA2H p.Asp35Tyr VAR_054893 rs121918217
2 FA2H p.Arg235Cys VAR_064621 rs387907039
3 FA2H p.Arg154Cys VAR_065245 rs387907040

Expression for Spastic Paraplegia 35, Autosomal Recessive

Search GEO for disease gene expression data for Spastic Paraplegia 35, Autosomal Recessive.

Pathways for Spastic Paraplegia 35, Autosomal Recessive

Pathways related to Spastic Paraplegia 35, Autosomal Recessive according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 9.95 PANK2 COASY

GO Terms for Spastic Paraplegia 35, Autosomal Recessive

Biological processes related to Spastic Paraplegia 35, Autosomal Recessive according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 lipid metabolic process GO:0006629 9.35 PNPLA6 PLA2G6 FA2H DDHD2 CYP7B1
2 lipid catabolic process GO:0016042 9.33 PNPLA6 PLA2G6 DDHD2
3 coenzyme A biosynthetic process GO:0015937 8.62 PANK2 COASY

Molecular functions related to Spastic Paraplegia 35, Autosomal Recessive according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 phosphatidylinositol-3,5-bisphosphate binding GO:0080025 9.16 WDR45 ATP13A2
2 lysophospholipase activity GO:0004622 8.96 PNPLA6 PLA2G6
3 phosphatidyl phospholipase B activity GO:0102545 8.62 PNPLA6 PLA2G6

Sources for Spastic Paraplegia 35, Autosomal Recessive

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 05-Mar-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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