SPG44
MCID: SPS096
MIFTS: 40

Spastic Paraplegia 44, Autosomal Recessive (SPG44)

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 44, Autosomal Recessive

MalaCards integrated aliases for Spastic Paraplegia 44, Autosomal Recessive:

Name: Spastic Paraplegia 44, Autosomal Recessive 57 72 29 13 6 70
Spg44 57 12 58 72
Hereditary Spastic Paraplegia 44 12 15
Paraplegia, Spastic, Type 44, Autosomal Recessive 39
Autosomal Recessive Spastic Paraplegia Type 44 58
Autosomal Recessive Spastic Paraplegia 44 12

Characteristics:

Orphanet epidemiological data:

58
autosomal recessive spastic paraplegia type 44
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Adolescent,Adult;

OMIM®:

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

Miscellaneous:
onset of mild symptoms in first or second decade
progression in adulthood
loss of independent ambulation (in 2 of 3 patients)
one family has been reported (last curated january 2010)


HPO:

31
spastic paraplegia 44, autosomal recessive:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 58  
Rare neurological diseases


Summaries for Spastic Paraplegia 44, Autosomal Recessive

UniProtKB/Swiss-Prot : 72 Spastic paraplegia 44, 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.

MalaCards based summary : Spastic Paraplegia 44, Autosomal Recessive, also known as spg44, is related to spastic ataxia 8 and hypomyelinating leukoencephalopathy, and has symptoms including action tremor and cerebellar ataxia. An important gene associated with Spastic Paraplegia 44, Autosomal Recessive is GJC2 (Gap Junction Protein Gamma 2). Affiliated tissues include eye, and related phenotypes are ataxia and dysarthria

Disease Ontology : 12 A hereditary spastic paraplegia that has material basis in mutation in the GJC2 gene on chromosome 1q42.

More information from OMIM: 613206 PS303350

Related Diseases for Spastic Paraplegia 44, 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 44, Autosomal Recessive via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 77)
# Related Disease Score Top Affiliating Genes
1 spastic ataxia 8 10.2 PLP1 GJC2
2 hypomyelinating leukoencephalopathy 10.2 PLP1 GJC2
3 leukodystrophy, hypomyelinating, 5 10.2 PLP1 GJC2
4 spastic paraplegia 49, autosomal recessive 10.2 SPG21 SPG11
5 spastic paraplegia 29, autosomal dominant 10.2 SPG21 SLC33A1
6 spastic paraplegia 27, autosomal recessive 10.2 SPG21 SLC33A1
7 spastic paraplegia 25, autosomal recessive 10.2 SPG21 SLC33A1
8 spastic paraplegia 19, autosomal dominant 10.2 SPG21 SLC33A1
9 spastic paraplegia 34, x-linked 10.2 SPG21 SLC33A1
10 spastic paraplegia 55, autosomal recessive 10.2 SPG21 SPG11
11 leukodystrophy, hypomyelinating, 7, with or without oligodontia and/or hypogonadotropic hypogonadism 10.2 PLP1 GJC2
12 leukodystrophy, hypomyelinating, 4 10.1 PLP1 GJC2
13 spastic paraplegia 28, autosomal recessive 10.1 SPG11 AP5Z1
14 spastic paraplegia 53, autosomal recessive 10.1 SLC33A1 AP5Z1
15 complex hereditary spastic paraplegia 10.1 SPG11 CYP7B1
16 pure hereditary spastic paraplegia 10.1 PLP1 ERLIN2
17 hereditary lymphedema ic 10.1 GJC2 GJB1
18 amyotrophic lateral sclerosis type 5 10.1 SPG11 AP5Z1
19 spastic paraplegia 57, autosomal recessive 10.1 SPG11 ERLIN2
20 hallermann-streiff syndrome 10.1 GJC2 GJB1
21 spastic paraplegia 5a, autosomal recessive 10.1 SPG11 CYP7B1
22 spastic paraplegia 50, autosomal recessive 10.1 SPG21 SPG11 AP5Z1
23 spastic paraplegia 61, autosomal recessive 10.1 SPG21 SPG11 AP5Z1
24 spastic paraplegia 54, autosomal recessive 10.1 SPG21 SPG11 AP5Z1
25 spastic paraplegia 11, autosomal recessive 10.1 SPG21 SPG11 AP5Z1
26 spastic paraplegia 16, x-linked 10.0 SPG21 SPG11 SLC33A1
27 spastic paraplegia 32, autosomal recessive 10.0 SPG21 SPG11 SLC33A1
28 spastic paraplegia 14, autosomal recessive 10.0 SPG21 SPG11 SLC33A1
29 charcot-marie-tooth disease type x 10.0 GJC2 GJB1
30 spastic paraplegia 62, autosomal recessive 10.0 PGAP1 ERLIN2
31 spastic paraplegia 64, autosomal recessive 10.0 SPG21 SPG11 PGAP1
32 spastic paraplegia 45, autosomal recessive 10.0 SPG21 SPG11 PGAP1
33 neuropathy, hereditary sensory, type iic 10.0 SPG21 SPG11 ERLIN2
34 charcot-marie-tooth disease, x-linked dominant, 1 10.0 GJC2 GJB1
35 hereditary neuropathies 9.9 PLP1 GJB1
36 hereditary spastic paraplegia 72 9.9 SPG11 ERLIN2 AP5Z1
37 spastic paraplegia 37, autosomal dominant 9.9 SPG21 SLC33A1 ERLIN2
38 palmoplantar keratoderma and congenital alopecia 1 9.9 GJC2 GJB1
39 pelizaeus-merzbacher-like disease 9.9 PLP1 GJC2 GJB1
40 spastic paraplegia 43, autosomal recessive 9.9 SPG11 SLC33A1 ERLIN2
41 leukodystrophy, hypomyelinating, 2 9.9 PLP1 GJC2 GJB1
42 hypomyelinating leukodystrophy 9.9 PLP1 GJC2 GJB1
43 oculodentodigital dysplasia 9.9 GJC2 GJB1
44 hereditary spastic paraplegia 51 9.8 SPG21 SPG11 PGAP1 AP5Z1
45 spastic paraplegia 52, autosomal recessive 9.8 SPG21 SPG11 PGAP1 AP5Z1
46 spastic paraplegia 56, autosomal recessive 9.8 SPG21 SPG11 PGAP1 AP5Z1
47 erythrokeratodermia variabilis et progressiva 1 9.8 GJC2 GJB1
48 spastic paraplegia 75, autosomal recessive 9.8 SLC33A1 PLP1 PGAP1 GJC2
49 spastic paraplegia 26, autosomal recessive 9.8 SPG21 SPG11 SLC33A1 PGAP1
50 mast syndrome 9.8 ZFYVE27 SPG21 SPG11

Graphical network of the top 20 diseases related to Spastic Paraplegia 44, Autosomal Recessive:



Diseases related to Spastic Paraplegia 44, Autosomal Recessive

Symptoms & Phenotypes for Spastic Paraplegia 44, Autosomal Recessive

Human phenotypes related to Spastic Paraplegia 44, Autosomal Recessive:

58 31 (show all 32)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 ataxia 58 31 hallmark (90%) Very frequent (99-80%) HP:0001251
2 dysarthria 58 31 hallmark (90%) Very frequent (99-80%) HP:0001260
3 abnormality of visual evoked potentials 58 31 hallmark (90%) Very frequent (99-80%) HP:0000649
4 strabismus 58 31 hallmark (90%) Very frequent (99-80%) HP:0000486
5 pes cavus 58 31 hallmark (90%) Very frequent (99-80%) HP:0001761
6 lower limb spasticity 58 31 hallmark (90%) Very frequent (99-80%) HP:0002061
7 cns hypomyelination 58 31 hallmark (90%) Very frequent (99-80%) HP:0003429
8 abnormal auditory evoked potentials 58 31 hallmark (90%) Very frequent (99-80%) HP:0006958
9 abnormal motor evoked potentials 58 31 hallmark (90%) Very frequent (99-80%) HP:0012896
10 abnormality of somatosensory evoked potentials 58 31 hallmark (90%) Very frequent (99-80%) HP:0007377
11 sensorineural hearing impairment 58 31 frequent (33%) Frequent (79-30%) HP:0000407
12 sensory impairment 58 31 frequent (33%) Frequent (79-30%) HP:0003474
13 difficulty walking 58 31 frequent (33%) Frequent (79-30%) HP:0002355
14 urinary bladder sphincter dysfunction 58 31 frequent (33%) Frequent (79-30%) HP:0002839
15 scoliosis 31 frequent (33%) HP:0002650
16 constipation 31 frequent (33%) HP:0002019
17 distal sensory impairment 31 frequent (33%) HP:0002936
18 urinary incontinence 31 frequent (33%) HP:0000020
19 seizure 31 frequent (33%) HP:0001250
20 delayed gross motor development 58 31 occasional (7.5%) Occasional (29-5%) HP:0002194
21 hypoplasia of the corpus callosum 31 very rare (1%) HP:0002079
22 seizures 58 Frequent (79-30%)
23 hyperreflexia 31 HP:0001347
24 cognitive impairment 31 HP:0100543
25 dysmetria 31 HP:0001310
26 spastic paraplegia 31 HP:0001258
27 babinski sign 31 HP:0003487
28 leukoencephalopathy 31 HP:0002352
29 intention tremor 31 HP:0002080
30 spastic gait 31 HP:0002064
31 slow saccadic eye movements 31 HP:0000514
32 upper limb spasticity 31 HP:0006986

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Neurologic Central Nervous System:
hyperreflexia
dysarthria
dysmetria
intention tremor
lower limb spasticity
more
Head And Neck Eyes:
slow saccades

Abdomen Gastrointestinal:
constipation (in 1 of 3 patients)

Skeletal Spine:
scoliosis (in 2 of 3 patients)

Skeletal Feet:
pes cavus

Head And Neck Ears:
sensorineural hearing loss (in 1 of 3 patients)

Genitourinary Bladder:
urinary incontinence (in 1 of 3 patients)

Neurologic Peripheral Nervous System:
decreased distal sensation (in 1 of 3 patients)

Clinical features from OMIM®:

613206 (Updated 05-Apr-2021)

UMLS symptoms related to Spastic Paraplegia 44, Autosomal Recessive:


action tremor; cerebellar ataxia

MGI Mouse Phenotypes related to Spastic Paraplegia 44, Autosomal Recessive:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 9.76 AP5Z1 GJB1 GJC2 PGAP1 PLP1 SLC33A1
2 cellular MP:0005384 9.56 AP5Z1 GJB1 GJC2 PGAP1 PLP1 SLC33A1
3 nervous system MP:0003631 9.23 AP5Z1 GJB1 GJC2 PGAP1 PLP1 SLC33A1

Drugs & Therapeutics for Spastic Paraplegia 44, Autosomal Recessive

Search Clinical Trials , NIH Clinical Center for Spastic Paraplegia 44, Autosomal Recessive

Genetic Tests for Spastic Paraplegia 44, Autosomal Recessive

Genetic tests related to Spastic Paraplegia 44, Autosomal Recessive:

# Genetic test Affiliating Genes
1 Spastic Paraplegia 44, Autosomal Recessive 29 GJC2

Anatomical Context for Spastic Paraplegia 44, Autosomal Recessive

MalaCards organs/tissues related to Spastic Paraplegia 44, Autosomal Recessive:

40
Eye

Publications for Spastic Paraplegia 44, Autosomal Recessive

Articles related to Spastic Paraplegia 44, Autosomal Recessive:

# Title Authors PMID Year
1
Hereditary spastic paraplegia is a novel phenotype for GJA12/GJC2 mutations. 57 6
19056803 2009
2
Late-onset phenotype associated with a homozygous GJC2 missense mutation in a Turkish family. 61
31431325 2019
3
Diseases of connexins expressed in myelinating glia. 61
28545922 2019
4
Inborn errors of brain myelin formation. 61
23622380 2013
5
Hereditary spastic paraplegias with autosomal dominant, recessive, X-linked, or maternal trait of inheritance. 61
22554690 2012
6
Pelizaeus-Merzbacher disease, Pelizaeus-Merzbacher-like disease 1, and related hypomyelinating disorders. 61
22422208 2012

Variations for Spastic Paraplegia 44, Autosomal Recessive

ClinVar genetic disease variations for Spastic Paraplegia 44, Autosomal Recessive:

6
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 GJC2 NM_020435.4(GJC2):c.108C>G (p.Ile36Met) SNV Pathogenic 2078 rs75469429 GRCh37: 1:228345567-228345567
GRCh38: 1:228157866-228157866
2 GJC2 NM_020435.4(GJC2):c.1134_1144del (p.Ala379fs) Deletion Pathogenic 656694 rs1571908452 GRCh37: 1:228346584-228346594
GRCh38: 1:228158883-228158893
3 GJC2 NM_020435.4(GJC2):c.550_566del (p.Ala184fs) Deletion Likely pathogenic 930587 GRCh37: 1:228346005-228346021
GRCh38: 1:228158304-228158320
4 GJC2 NM_020435.4(GJC2):c.1234C>T (p.His412Tyr) SNV Uncertain significance 445910 rs200334298 GRCh37: 1:228346693-228346693
GRCh38: 1:228158992-228158992
5 GJC2 NM_020435.4(GJC2):c.1254_1258delinsCG (p.Lys418_Arg420delinsAsnGly) Indel not provided 441072 rs1553262641 GRCh37: 1:228346713-228346717
GRCh38: 1:228159012-228159016

UniProtKB/Swiss-Prot genetic disease variations for Spastic Paraplegia 44, Autosomal Recessive:

72
# Symbol AA change Variation ID SNP ID
1 GJC2 p.Ile36Met VAR_063172 rs75469429

Expression for Spastic Paraplegia 44, Autosomal Recessive

Search GEO for disease gene expression data for Spastic Paraplegia 44, Autosomal Recessive.

Pathways for Spastic Paraplegia 44, Autosomal Recessive

GO Terms for Spastic Paraplegia 44, Autosomal Recessive

Cellular components related to Spastic Paraplegia 44, Autosomal Recessive according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 endoplasmic reticulum GO:0005783 9.72 ZFYVE27 SLC33A1 PGAP1 ERLIN2 CYP7B1
2 myelin sheath GO:0043209 9.26 PLP1 GJC2
3 gap junction GO:0005921 9.16 GJC2 GJB1
4 endoplasmic reticulum membrane GO:0005789 9.1 ZFYVE27 SLC33A1 PGAP1 GJB1 ERLIN2 CYP7B1
5 connexin complex GO:0005922 8.96 GJC2 GJB1

Biological processes related to Spastic Paraplegia 44, Autosomal Recessive according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 transmembrane transport GO:0055085 9.26 SLC33A1 GJC2 GJB1 ERLIN2
2 cell communication GO:0007154 9.16 GJC2 GJB1
3 positive regulation of calcium ion transmembrane transport GO:1904427 8.62 PLP1 GJC2

Molecular functions related to Spastic Paraplegia 44, Autosomal Recessive according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 gap junction channel activity GO:0005243 8.62 GJC2 GJB1

Sources for Spastic Paraplegia 44, 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-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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