MCID: SPN308
MIFTS: 39

Spinocerebellar Ataxia 28

Categories: Genetic diseases, Rare diseases, Neuronal diseases, Metabolic diseases, Skin diseases, Eye diseases, Mental diseases, Ear diseases, Fetal diseases, Liver diseases

Aliases & Classifications for Spinocerebellar Ataxia 28

MalaCards integrated aliases for Spinocerebellar Ataxia 28:

Name: Spinocerebellar Ataxia 28 57 53 75 29 13 6 73
Spinocerebellar Ataxia Type 28 12 24 53 59 15
Sca28 57 24 53 59 75
Ataxia, Spinocerebellar, Type 28 40

Characteristics:

Orphanet epidemiological data:

59
spinocerebellar ataxia type 28
Inheritance: Autosomal dominant; Age of onset: Childhood;

OMIM:

57
Inheritance:
autosomal dominant

Miscellaneous:
slow progression
mean age at onset 30.7 years (range 6 to 60 years)


HPO:

32
spinocerebellar ataxia 28:
Onset and clinical course slow progression
Inheritance autosomal dominant inheritance


GeneReviews:

24
Penetrance From the studies of sca28 published to date, disease penetrance appears to be complete...

Classifications:



External Ids:

OMIM 57 610246
Disease Ontology 12 DOID:0050977
Orphanet 59 ORPHA101109
MESH via Orphanet 45 C537205
UMLS via Orphanet 74 C1853249
ICD10 via Orphanet 34 G11.1
MedGen 42 C1853249
MeSH 44 D020754
UMLS 73 C1853249

Summaries for Spinocerebellar Ataxia 28

NIH Rare Diseases : 53 Spinocerebellar ataxia 28 (SCA28)is a slowly progressive movement disorder that typically begins in early adulthood (but can affect children and older adults as well). Early signs and symptoms include problems with coordination and balance when walking (gait ataxia), speech and swallowing difficulties (dysarthria), over-reactive reflex reactions in knees and ankles (hyperreflexia), weakness in the muscles that control eye movement (ophthalmoparesis), uncontrolled movement of the eye (nystagmus) and drooping eyelid (ptosis). The symptoms worsen very slowly over time. SCA28 is caused by changes in the AFG3L2 gene and is inherited in an autosomal dominant fashion. There is currently not a cure for SCA28, but treatments are available to help manage symptoms.

MalaCards based summary : Spinocerebellar Ataxia 28, also known as spinocerebellar ataxia type 28, is related to autosomal dominant cerebellar ataxia and spastic ataxia 5, and has symptoms including muscle spasticity and gait ataxia. An important gene associated with Spinocerebellar Ataxia 28 is AFG3L2 (AFG3 Like Matrix AAA Peptidase Subunit 2), and among its related pathways/superpathways is Long-term depression. Affiliated tissues include eye, spinal cord and cerebellum, and related phenotypes are dysarthria and gait ataxia

UniProtKB/Swiss-Prot : 75 Spinocerebellar ataxia 28: Spinocerebellar ataxia is a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA28 is an autosomal dominant cerebellar ataxia (ADCA) with a slow progressive course and no evidence of sensory involvement or cognitive impairment.

Description from OMIM: 610246
GeneReviews: NBK54582

Related Diseases for Spinocerebellar Ataxia 28

Diseases in the Spinocerebellar Ataxia 2 family:

Spinocerebellar Ataxia 31 Spinocerebellar Ataxia 29
Spinocerebellar Ataxia 34 Spinocerebellar Ataxia 1
Spinocerebellar Ataxia 7 Spinocerebellar Ataxia 6
Spinocerebellar Ataxia, Autosomal Recessive 2 Spinocerebellar Ataxia, Autosomal Recessive 3
Spinocerebellar Ataxia 4 Spinocerebellar Ataxia 5
Spinocerebellar Ataxia 10 Spinocerebellar Ataxia 12
Spinocerebellar Ataxia 11 Spinocerebellar Ataxia 13
Spinocerebellar Ataxia 14 Spinocerebellar Ataxia, Autosomal Recessive 1
Spinocerebellar Ataxia 15 Spinocerebellar Ataxia 17
Spinocerebellar Ataxia, Autosomal Recessive 4 Spinocerebellar Ataxia 19
Spinocerebellar Ataxia 21 Spinocerebellar Ataxia 18
Spinocerebellar Ataxia, Autosomal Recessive 6 Spinocerebellar Ataxia 20
Spinocerebellar Ataxia 25 Spinocerebellar Ataxia 8
Spinocerebellar Ataxia, Autosomal Recessive 7 Spinocerebellar Ataxia 26
Spinocerebellar Ataxia 27 Spinocerebellar Ataxia 23
Spinocerebellar Ataxia 28 Spinocerebellar Ataxia, Autosomal Recessive 8
Spinocerebellar Ataxia 9 Spinocerebellar Ataxia 30
Spinocerebellar Ataxia, Autosomal Recessive 10 Spinocerebellar Ataxia 35
Spinocerebellar Ataxia 32 Spinocerebellar Ataxia 36
Spinocerebellar Ataxia, Autosomal Recessive 11 Spinocerebellar Ataxia, Autosomal Recessive 12
Spinocerebellar Ataxia, Autosomal Recessive 13 Spinocerebellar Ataxia, Autosomal Recessive 14
Spinocerebellar Ataxia, Autosomal Recessive 15 Spinocerebellar Ataxia, Autosomal Recessive 16
Spinocerebellar Ataxia 37 Spinocerebellar Ataxia 38
Spinocerebellar Ataxia 40 Spinocerebellar Ataxia, Autosomal Recessive 17
Spinocerebellar Ataxia, Autosomal Recessive 18 Spinocerebellar Ataxia, Autosomal Recessive 20
Spinocerebellar Ataxia 41 Spinocerebellar Ataxia, Autosomal Recessive 21
Spinocerebellar Ataxia 42 Spinocerebellar Ataxia, Autosomal Recessive 22
Spinocerebellar Ataxia, Autosomal Recessive 23 Spinocerebellar Ataxia 43
Spinocerebellar Ataxia, Autosomal Recessive 24 Spinocerebellar Ataxia, Autosomal Recessive 25
Spinocerebellar Ataxia, Autosomal Recessive 26 Spinocerebellar Ataxia 44
Spinocerebellar Ataxia 45 Spinocerebellar Ataxia 46
Spinocerebellar Ataxia 47 Spinocerebellar Ataxia Type 16
Spinocerebellar Ataxia Type 19/22 Grid2-Related Spinocerebellar Ataxia
Spinocerebellar Ataxia Autosomal Recessive 5

Diseases related to Spinocerebellar Ataxia 28 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 13)
# Related Disease Score Top Affiliating Genes
1 autosomal dominant cerebellar ataxia 27.0 AFG3L2 FGF14 KCNC3 PDYN PRKCG TTBK2
2 spastic ataxia 5 10.5 AFG3L2 LOC107985154
3 spastic ataxia 5, autosomal recessive 10.5 AFG3L2 LOC107985154
4 spinocerebellar ataxia 11 10.0 PRKCG TTBK2
5 spastic paraplegia 7, autosomal recessive 9.9 AFG3L2 IMPACT SPG7
6 spinocerebellar ataxia 15 9.8 KCNC3 PDYN
7 spastic ataxia 9.8 AFG3L2 SPG7
8 spinocerebellar ataxia 27 9.7 FGF14 GRM1
9 spastic paraplegia 73, autosomal dominant 9.6 GRM1 SPG7
10 spastic paraplegia 76, autosomal recessive 9.6 GRM1 SPG7
11 cerebellar disease 9.5 PDYN PRKCG
12 hereditary ataxia 9.3 AFG3L2 KCNC3 PRKCG SPG7
13 aceruloplasminemia 9.3 KCNC3 PDYN PRKCG

Graphical network of the top 20 diseases related to Spinocerebellar Ataxia 28:



Diseases related to Spinocerebellar Ataxia 28

Symptoms & Phenotypes for Spinocerebellar Ataxia 28

Symptoms via clinical synopsis from OMIM:

57
Neurologic Central Nervous System:
spasticity
dysarthria
gait ataxia
limb ataxia
cerebellar atrophy
more
Head And Neck Eyes:
gaze-evoked nystagmus
dysmetric saccades
eye movement abnormalities
smooth pursuit abnormalities
slow saccades (with longer disease duration)
more

Clinical features from OMIM:

610246

Human phenotypes related to Spinocerebellar Ataxia 28:

59 32 (show all 24)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 dysarthria 59 32 hallmark (90%) Very frequent (99-80%) HP:0001260
2 gait ataxia 59 32 hallmark (90%) Very frequent (99-80%) HP:0002066
3 limb ataxia 59 32 hallmark (90%) Very frequent (99-80%) HP:0002070
4 lower limb hyperreflexia 59 32 hallmark (90%) Very frequent (99-80%) HP:0002395
5 ptosis 59 32 frequent (33%) Frequent (79-30%) HP:0000508
6 slow saccadic eye movements 59 32 frequent (33%) Frequent (79-30%) HP:0000514
7 ophthalmoparesis 59 32 frequent (33%) Frequent (79-30%) HP:0000597
8 nystagmus 59 32 frequent (33%) Frequent (79-30%) HP:0000639
9 babinski sign 59 32 frequent (33%) Frequent (79-30%) HP:0003487
10 parkinsonism 59 32 occasional (7.5%) Occasional (29-5%) HP:0001300
11 kinetic tremor 59 32 occasional (7.5%) Occasional (29-5%) HP:0030186
12 depressivity 59 32 very rare (1%) Very rare (<4-1%) HP:0000716
13 spasticity 59 32 very rare (1%) Very rare (<4-1%) HP:0001257
14 dystonia 59 32 occasional (7.5%) Very rare (<4-1%) HP:0001332
15 rigidity 59 32 very rare (1%) Very rare (<4-1%) HP:0002063
16 head tremor 59 32 very rare (1%) Very rare (<4-1%) HP:0002346
17 memory impairment 59 32 very rare (1%) Very rare (<4-1%) HP:0002354
18 limb dystonia 59 32 very rare (1%) Very rare (<4-1%) HP:0002451
19 behavioral abnormality 59 Very rare (<4-1%)
20 cognitive impairment 59 Very rare (<4-1%)
21 gaze-evoked nystagmus 32 HP:0000640
22 dysmetric saccades 32 HP:0000641
23 cerebellar atrophy 32 HP:0001272
24 hypertonia 32 HP:0001276

UMLS symptoms related to Spinocerebellar Ataxia 28:


muscle spasticity, gait ataxia

MGI Mouse Phenotypes related to Spinocerebellar Ataxia 28:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 9.7 AFG3L2 FGF14 GRM1 KCNC3 PDYN PRKCG
2 growth/size/body region MP:0005378 9.5 AFG3L2 FGF14 GRM1 KCNC3 PDYN SPG7
3 nervous system MP:0003631 9.23 GRM1 KCNC3 PDYN PRKCG SPG7 TTBK2

Drugs & Therapeutics for Spinocerebellar Ataxia 28

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford Recruiting NCT01793168

Search NIH Clinical Center for Spinocerebellar Ataxia 28

Genetic Tests for Spinocerebellar Ataxia 28

Genetic tests related to Spinocerebellar Ataxia 28:

# Genetic test Affiliating Genes
1 Spinocerebellar Ataxia 28 29 AFG3L2

Anatomical Context for Spinocerebellar Ataxia 28

MalaCards organs/tissues related to Spinocerebellar Ataxia 28:

41
Eye, Spinal Cord, Cerebellum

Publications for Spinocerebellar Ataxia 28

Articles related to Spinocerebellar Ataxia 28:

# Title Authors Year
1
Spinocerebellar ataxia 28: a novel AFG3L2 mutation in a German family with young onset, slow progression and saccadic slowing. ( 26677414 )
2015

Variations for Spinocerebellar Ataxia 28

UniProtKB/Swiss-Prot genetic disease variations for Spinocerebellar Ataxia 28:

75 (show all 13)
# Symbol AA change Variation ID SNP ID
1 AFG3L2 p.Asn432Thr VAR_063544 rs151344512
2 AFG3L2 p.Glu691Lys VAR_063545 rs151344520
3 AFG3L2 p.Ala694Glu VAR_063546 rs151344521
4 AFG3L2 p.Arg702Gln VAR_063547 rs151344523
5 AFG3L2 p.Thr654Ile VAR_064402 rs151344513
6 AFG3L2 p.Met666Arg VAR_064403 rs151344515
7 AFG3L2 p.Met666Thr VAR_064404 rs151344515
8 AFG3L2 p.Met666Val VAR_064405 rs151344514
9 AFG3L2 p.Gly671Glu VAR_064406 rs151344518
10 AFG3L2 p.Gly671Arg VAR_064407 rs151344517
11 AFG3L2 p.Glu700Lys VAR_064408 rs151344522
12 AFG3L2 p.Tyr689His VAR_075198
13 AFG3L2 p.Tyr689Asn VAR_075199

ClinVar genetic disease variations for Spinocerebellar Ataxia 28:

6
(show all 24)
# Gene Variation Type Significance SNP ID Assembly Location
1 AFG3L2 NM_006796.2(AFG3L2): c.2071G> A (p.Glu691Lys) single nucleotide variant Pathogenic rs151344520 GRCh37 Chromosome 18, 12337444: 12337444
2 AFG3L2 NM_006796.2(AFG3L2): c.2071G> A (p.Glu691Lys) single nucleotide variant Pathogenic rs151344520 GRCh38 Chromosome 18, 12337445: 12337445
3 AFG3L2 NM_006796.2(AFG3L2): c.2021_2022delCCinsTA (p.Ser674Leu) indel Pathogenic rs151344519 GRCh37 Chromosome 18, 12337493: 12337494
4 AFG3L2 NM_006796.2(AFG3L2): c.2021_2022delCCinsTA (p.Ser674Leu) indel Pathogenic rs151344519 GRCh38 Chromosome 18, 12337494: 12337495
5 AFG3L2 NM_006796.2(AFG3L2): c.2081C> A (p.Ala694Glu) single nucleotide variant Pathogenic rs151344521 GRCh37 Chromosome 18, 12337434: 12337434
6 AFG3L2 NM_006796.2(AFG3L2): c.2081C> A (p.Ala694Glu) single nucleotide variant Pathogenic rs151344521 GRCh38 Chromosome 18, 12337435: 12337435
7 AFG3L2 NM_006796.2(AFG3L2): c.2105G> A (p.Arg702Gln) single nucleotide variant Pathogenic/Likely pathogenic rs151344523 GRCh37 Chromosome 18, 12337410: 12337410
8 AFG3L2 NM_006796.2(AFG3L2): c.2105G> A (p.Arg702Gln) single nucleotide variant Pathogenic/Likely pathogenic rs151344523 GRCh38 Chromosome 18, 12337411: 12337411
9 AFG3L2 NM_006796.2(AFG3L2): c.1295A> C (p.Asn432Thr) single nucleotide variant Pathogenic rs151344512 GRCh37 Chromosome 18, 12353027: 12353027
10 AFG3L2 NM_006796.2(AFG3L2): c.1295A> C (p.Asn432Thr) single nucleotide variant Pathogenic rs151344512 GRCh38 Chromosome 18, 12353028: 12353028
11 AFG3L2 NM_006796.2(AFG3L2): c.1996A> G (p.Met666Val) single nucleotide variant Pathogenic rs151344514 GRCh37 Chromosome 18, 12337519: 12337519
12 AFG3L2 NM_006796.2(AFG3L2): c.1996A> G (p.Met666Val) single nucleotide variant Pathogenic rs151344514 GRCh38 Chromosome 18, 12337520: 12337520
13 AFG3L2 NM_006796.2(AFG3L2): c.1997T> G (p.Met666Arg) single nucleotide variant Pathogenic rs151344515 GRCh37 Chromosome 18, 12337518: 12337518
14 AFG3L2 NM_006796.2(AFG3L2): c.1997T> G (p.Met666Arg) single nucleotide variant Pathogenic rs151344515 GRCh38 Chromosome 18, 12337519: 12337519
15 AFG3L2 NM_006796.2(AFG3L2): c.2011G> A (p.Gly671Arg) single nucleotide variant Pathogenic rs151344517 GRCh37 Chromosome 18, 12337504: 12337504
16 AFG3L2 NM_006796.2(AFG3L2): c.2011G> A (p.Gly671Arg) single nucleotide variant Pathogenic rs151344517 GRCh38 Chromosome 18, 12337505: 12337505
17 AFG3L2 NM_006796.2(AFG3L2): c.1961C> T (p.Thr654Ile) single nucleotide variant Pathogenic rs151344513 GRCh37 Chromosome 18, 12340219: 12340219
18 AFG3L2 NM_006796.2(AFG3L2): c.1961C> T (p.Thr654Ile) single nucleotide variant Pathogenic rs151344513 GRCh38 Chromosome 18, 12340220: 12340220
19 AFG3L2 NM_006796.2(AFG3L2): c.1997T> C (p.Met666Thr) single nucleotide variant Pathogenic rs151344515 GRCh37 Chromosome 18, 12337518: 12337518
20 AFG3L2 NM_006796.2(AFG3L2): c.1997T> C (p.Met666Thr) single nucleotide variant Pathogenic rs151344515 GRCh38 Chromosome 18, 12337519: 12337519
21 AFG3L2 NM_006796.2(AFG3L2): c.2012G> A (p.Gly671Glu) single nucleotide variant Pathogenic rs151344518 GRCh37 Chromosome 18, 12337503: 12337503
22 AFG3L2 NM_006796.2(AFG3L2): c.2012G> A (p.Gly671Glu) single nucleotide variant Pathogenic rs151344518 GRCh38 Chromosome 18, 12337504: 12337504
23 AFG3L2 NM_006796.2(AFG3L2): c.2098G> A (p.Glu700Lys) single nucleotide variant Pathogenic rs151344522 GRCh37 Chromosome 18, 12337417: 12337417
24 AFG3L2 NM_006796.2(AFG3L2): c.2098G> A (p.Glu700Lys) single nucleotide variant Pathogenic rs151344522 GRCh38 Chromosome 18, 12337418: 12337418

Expression for Spinocerebellar Ataxia 28

Search GEO for disease gene expression data for Spinocerebellar Ataxia 28.

Pathways for Spinocerebellar Ataxia 28

Pathways related to Spinocerebellar Ataxia 28 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 10.4 GRM1 PRKCG

GO Terms for Spinocerebellar Ataxia 28

Cellular components related to Spinocerebellar Ataxia 28 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 dendrite GO:0030425 9.26 GRM1 KCNC3 PDYN PRKCG
2 presynaptic membrane GO:0042734 9.16 GRM1 KCNC3
3 m-AAA complex GO:0005745 8.62 AFG3L2 SPG7

Biological processes related to Spinocerebellar Ataxia 28 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 chemical synaptic transmission GO:0007268 9.13 GRM1 PDYN PRKCG
2 mitochondrial calcium ion transmembrane transport GO:0006851 8.62 AFG3L2 SPG7

Sources for Spinocerebellar Ataxia 28

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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