SCAR12
MCID: SPN264
MIFTS: 35

Spinocerebellar Ataxia, Autosomal Recessive 12 (SCAR12)

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

Aliases & Classifications for Spinocerebellar Ataxia, Autosomal Recessive 12

MalaCards integrated aliases for Spinocerebellar Ataxia, Autosomal Recessive 12:

Name: Spinocerebellar Ataxia, Autosomal Recessive 12 56 29 13 6 71
Scar12 56 58 73
Autosomal Recessive Spinocerebellar Ataxia 12 12 15
Autosomal Recessive Cerebellar Ataxia-Epilepsy-Intellectual Disability Syndrome Due to Wwox Deficiency 58
Spinocerebellar Ataxia with Mental Retardation and Epilepsy 56
Ataxia, Spinocerebellar, Autosomal Recessive, Type 12 39
Autosomal Recessive Spinocerebellar Ataxia Type 12 58
Spinocerebellar Ataxia, Autosomal Recessive, 12 73

Characteristics:

Orphanet epidemiological data:

58
autosomal recessive cerebellar ataxia-epilepsy-intellectual disability syndrome due to wwox deficiency
Inheritance: Autosomal recessive; Age of onset: Infancy,Neonatal;

OMIM:

56
Inheritance:
autosomal recessive

Miscellaneous:
onset of seizures between 9 and 12 months of age
two unrelated consanguineous families (saudi arabian and israeli palestinian) have been reported (last curated february 2014)


HPO:

31
spinocerebellar ataxia, autosomal recessive 12:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 58  
Rare neurological diseases


Summaries for Spinocerebellar Ataxia, Autosomal Recessive 12

UniProtKB/Swiss-Prot : 73 Spinocerebellar ataxia, autosomal recessive, 12: A form of spinocerebellar ataxia, 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. SCAR12 is additionally characterized by onset of generalized seizures in infancy, and delayed psychomotor development with mental retardation. Some patients may also show spasticity.

MalaCards based summary : Spinocerebellar Ataxia, Autosomal Recessive 12, also known as scar12, is related to epileptic encephalopathy, early infantile, 1 and anterior segment dysgenesis, and has symptoms including seizures, gait ataxia and cerebellar ataxia. An important gene associated with Spinocerebellar Ataxia, Autosomal Recessive 12 is WWOX (WW Domain Containing Oxidoreductase). Affiliated tissues include eye, cerebellum and spinal cord, and related phenotypes are delayed speech and language development and nystagmus

Disease Ontology : 12 An autosomal recessive cerebellar ataxia that is characterized by onset of generalized seizures in infancy, delayed psychomotor development with mental retardation, and cerebellar ataxia and that has material basis in homozygous mutation in the WWOX gene on chromosome 16q23.

OMIM : 56 Autosomal recessive spinocerebellar ataxia-12 is a neurologic disorder characterized by onset of generalized seizures in infancy, delayed psychomotor development with mental retardation, and cerebellar ataxia. Some patients may also show spasticity (summary by Mallaret et al., 2014). (614322)

Related Diseases for Spinocerebellar Ataxia, Autosomal Recessive 12

Diseases in the Spinocerebellar Ataxia 6 family:

Spinocerebellar Ataxia 31 Spinocerebellar Ataxia 29
Spinocerebellar Ataxia 34 Spinocerebellar Ataxia 1
Spinocerebellar Ataxia 7 Spinocerebellar Ataxia 2
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 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 48 Spinocerebellar Ataxia, Autosomal Recessive 27
Spinocerebellar Ataxia, Autosomal Recessive 28 Spinocerebellar Ataxia Type 19/22
Grid2-Related Spinocerebellar Ataxia Spinocerebellar Ataxia Autosomal Recessive 5

Diseases related to Spinocerebellar Ataxia, Autosomal Recessive 12 via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 epileptic encephalopathy, early infantile, 1 9.8 WWOX MAF
2 anterior segment dysgenesis 9.5 TENM3 MAF

Symptoms & Phenotypes for Spinocerebellar Ataxia, Autosomal Recessive 12

Human phenotypes related to Spinocerebellar Ataxia, Autosomal Recessive 12:

58 31 (show all 19)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 delayed speech and language development 58 31 hallmark (90%) Very frequent (99-80%) HP:0000750
2 nystagmus 58 31 hallmark (90%) Very frequent (99-80%) HP:0000639
3 motor delay 58 31 hallmark (90%) Very frequent (99-80%) HP:0001270
4 dysarthria 58 31 hallmark (90%) Very frequent (99-80%) HP:0001260
5 hyporeflexia 58 31 hallmark (90%) Very frequent (99-80%) HP:0001265
6 gait ataxia 58 31 hallmark (90%) Very frequent (99-80%) HP:0002066
7 limb ataxia 58 31 hallmark (90%) Very frequent (99-80%) HP:0002070
8 urinary bladder sphincter dysfunction 58 31 occasional (7.5%) Occasional (29-5%) HP:0002839
9 optic atrophy 31 occasional (7.5%) HP:0000648
10 spasticity 31 occasional (7.5%) HP:0001257
11 growth delay 31 occasional (7.5%) HP:0001510
12 babinski sign 31 occasional (7.5%) HP:0003487
13 retinal degeneration 31 occasional (7.5%) HP:0000546
14 intellectual disability 31 HP:0001249
15 global developmental delay 31 HP:0001263
16 microcephaly 31 HP:0000252
17 cerebellar atrophy 31 HP:0001272
18 gaze-evoked nystagmus 31 HP:0000640
19 seizure 31 HP:0001250

Symptoms via clinical synopsis from OMIM:

56
Neurologic Central Nervous System:
seizures
dysarthria
gait ataxia
limb ataxia
cerebellar ataxia
more
Head And Neck Eyes:
gaze-evoked nystagmus

Neurologic Peripheral Nervous System:
hyporeflexia

Clinical features from OMIM:

614322

UMLS symptoms related to Spinocerebellar Ataxia, Autosomal Recessive 12:


seizures, gait ataxia, cerebellar ataxia

Drugs & Therapeutics for Spinocerebellar Ataxia, Autosomal Recessive 12

Search Clinical Trials , NIH Clinical Center for Spinocerebellar Ataxia, Autosomal Recessive 12

Genetic Tests for Spinocerebellar Ataxia, Autosomal Recessive 12

Genetic tests related to Spinocerebellar Ataxia, Autosomal Recessive 12:

# Genetic test Affiliating Genes
1 Spinocerebellar Ataxia, Autosomal Recessive 12 29 WWOX

Anatomical Context for Spinocerebellar Ataxia, Autosomal Recessive 12

MalaCards organs/tissues related to Spinocerebellar Ataxia, Autosomal Recessive 12:

40
Eye, Cerebellum, Spinal Cord

Publications for Spinocerebellar Ataxia, Autosomal Recessive 12

Articles related to Spinocerebellar Ataxia, Autosomal Recessive 12:

# Title Authors PMID Year
1
The tumour suppressor gene WWOX is mutated in autosomal recessive cerebellar ataxia with epilepsy and mental retardation. 56 6
24369382 2014
2
A new form of childhood onset, autosomal recessive spinocerebellar ataxia and epilepsy is localized at 16q21-q23. 6 56
17470496 2007
3
Novel compound heterozygous mutations in the WWOX gene cause early infantile epileptic encephalopathy. 61
31669195 2019
4
Wwox deletion leads to reduced GABA-ergic inhibitory interneuron numbers and activation of microglia and astrocytes in mouse hippocampus. 61
30290271 2019
5
WWOX-associated encephalopathies: identification of the phenotypic spectrum and the resulting genotype-phenotype correlation. 61
30094525 2018
6
WWOX and severe autosomal recessive epileptic encephalopathy: first case in the prenatal period. 61
25716914 2015

Variations for Spinocerebellar Ataxia, Autosomal Recessive 12

ClinVar genetic disease variations for Spinocerebellar Ataxia, Autosomal Recessive 12:

6 (show top 50) (show all 246) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 WWOX duplication Pathogenic 473015 16:78318746-78386940
2 WWOX NC_000016.10:g.(?_78432468)_(78432772_?)deldeletion Pathogenic 540247 16:78466365-78466669 16:78432468-78432772
3 WWOX NC_000016.10:g.(?_78386840)_(78386968_?)deldeletion Pathogenic 583631 16:78420737-78420865 16:78386840-78386968
4 WWOX NC_000016.10:g.(?_78164163)_(78164309_?)deldeletion Pathogenic 584160 16:78198060-78198206 16:78164163-78164309
5 WWOX NC_000016.10:g.(?_79211588)_(79211816_?)deldeletion Pathogenic 657908 16:79245485-79245713 16:79211588-79211816
6 WWOX NC_000016.10:g.(?_78424850)_(78432772_?)deldeletion Pathogenic 832198 16:78458747-78466669
7 WWOX NM_016373.4(WWOX):c.107+1G>ASNV Pathogenic 689796 16:78133783-78133783 16:78099886-78099886
8 WWOX NC_000016.10:g.(?_78099759)_(78099909_?)deldeletion Pathogenic 831561 16:78133656-78133806
9 WWOX NC_000016.10:g.(?_78099759)_(78115174_?)deldeletion Pathogenic 830545 16:78133656-78149071
10 WWOX NC_000016.10:g.(?_78099759)_(78432772_?)deldeletion Pathogenic 832849 16:78133656-78466669
11 WWOX NC_000016.10:g.(?_78278583)_(78386968_?)deldeletion Pathogenic 833164 16:78312480-78420865
12 WWOX NM_016373.4(WWOX):c.1114G>C (p.Gly372Arg)SNV Pathogenic 100648 rs587777127 16:79245562-79245562 16:79211665-79211665
13 WWOX NM_016373.4(WWOX):c.139C>A (p.Pro47Thr)SNV Pathogenic 100649 rs587777128 16:78142351-78142351 16:78108454-78108454
14 WWOX NM_016373.4(WWOX):c.160C>T (p.Arg54Ter)SNV Pathogenic 120325 rs587777248 16:78142372-78142372 16:78108475-78108475
15 WWOX NM_016373.4(WWOX):c.779C>G (p.Ser260Ter)SNV Pathogenic 241104 rs878855021 16:78458940-78458940 16:78425043-78425043
16 WWOX NM_016373.4(WWOX):c.790C>T (p.Arg264Ter)SNV Pathogenic 241105 rs756762196 16:78458951-78458951 16:78425054-78425054
17 WWOX NM_016373.4(WWOX):c.583G>T (p.Glu195Ter)SNV Pathogenic/Likely pathogenic 568364 rs1567542020 16:78420823-78420823 16:78386926-78386926
18 WWOX NM_016373.4(WWOX):c.214C>T (p.Gln72Ter)SNV Pathogenic/Likely pathogenic 449920 rs201008667 16:78143716-78143716 16:78109819-78109819
19 WWOX NM_016373.4(WWOX):c.409+1G>CSNV Likely pathogenic 410092 rs1060502727 16:78149052-78149052 16:78115155-78115155
20 WWOX NC_000016.10:g.(?_78424850)_(78425075_?)deldeletion Likely pathogenic 473016 16:78424850-78425075
21 WWOX NC_000016.9:g.(?_78458747)_(78466669_?)dupduplication Likely pathogenic 583590 16:78458747-78466669 16:78424850-78432772
22 WWOX NC_000016.10:g.(?_78386840)_(78432772_?)deldeletion Likely pathogenic 584296 16:78420737-78466669 16:78386840-78432772
23 WWOX NM_016373.4(WWOX):c.511G>T (p.Glu171Ter)SNV Likely pathogenic 225517 rs751181600 16:78198181-78198181 16:78164284-78164284
24 WWOX NM_016373.4(WWOX):c.108-2A>TSNV Likely pathogenic 804478 16:78142318-78142318 16:78108421-78108421
25 WWOX NC_000016.10:g.(?_78278583)_(78432772_?)deldeletion Likely pathogenic 832075 16:78312480-78466669
26 WWOX NM_016373.4(WWOX):c.885G>A (p.Arg295=)SNV Conflicting interpretations of pathogenicity 212617 rs79771882 16:78466478-78466478 16:78432581-78432581
27 WWOX NM_016373.4(WWOX):c.816G>T (p.Leu272Phe)SNV Conflicting interpretations of pathogenicity 241106 rs186745328 16:78466409-78466409 16:78432512-78432512
28 WWOX NM_016373.4(WWOX):c.517-10C>GSNV Conflicting interpretations of pathogenicity 385828 rs199820033 16:78420747-78420747 16:78386850-78386850
29 WWOX NM_016373.4(WWOX):c.332C>G (p.Thr111Ser)SNV Conflicting interpretations of pathogenicity 383820 rs114755364 16:78148974-78148974 16:78115077-78115077
30 WWOX NM_016373.4(WWOX):c.410-3T>CSNV Conflicting interpretations of pathogenicity 388457 rs201178351 16:78198077-78198077 16:78164180-78164180
31 WWOX NM_016373.4(WWOX):c.1146C>T (p.Cys382=)SNV Conflicting interpretations of pathogenicity 384388 rs780939546 16:79245594-79245594 16:79211697-79211697
32 WWOX NM_016373.4(WWOX):c.315A>G (p.Gln105=)SNV Conflicting interpretations of pathogenicity 507069 rs752822745 16:78148957-78148957 16:78115060-78115060
33 WWOX NM_016373.4(WWOX):c.421G>A (p.Ala141Thr)SNV Conflicting interpretations of pathogenicity 410088 rs369907002 16:78198091-78198091 16:78164194-78164194
34 WWOX NM_016373.4(WWOX):c.1178C>T (p.Thr393Met)SNV Conflicting interpretations of pathogenicity 410084 rs139253468 16:79245626-79245626 16:79211729-79211729
35 WWOX NM_016373.4(WWOX):c.1115G>A (p.Gly372Glu)SNV Conflicting interpretations of pathogenicity 419331 rs1064793798 16:79245563-79245563 16:79211666-79211666
36 WWOX NM_016373.4(WWOX):c.605+5G>ASNV Conflicting interpretations of pathogenicity 450592 rs1039151413 16:78420850-78420850 16:78386953-78386953
37 WWOX NM_016373.4(WWOX):c.468G>T (p.Arg156Ser)SNV Conflicting interpretations of pathogenicity 415952 rs140817689 16:78198138-78198138 16:78164241-78164241
38 WWOX NM_016373.4(WWOX):c.513A>G (p.Glu171=)SNV Uncertain significance 410093 rs1060502728 16:78198183-78198183 16:78164286-78164286
39 WWOX NC_000016.9:g.(?_78133656)_(78466669_?)dupduplication Uncertain significance 473014 16:78133656-78466669
40 WWOX NM_016373.4(WWOX):c.385G>C (p.Val129Leu)SNV Uncertain significance 473023 rs781732002 16:78149027-78149027 16:78115130-78115130
41 WWOX NM_016373.4(WWOX):c.406A>G (p.Ile136Val)SNV Uncertain significance 473024 rs193027041 16:78149048-78149048 16:78115151-78115151
42 WWOX NM_016373.4(WWOX):c.535G>T (p.Ala179Ser)SNV Uncertain significance 473027 rs11545029 16:78420775-78420775 16:78386878-78386878
43 WWOX NM_016373.4(WWOX):c.568G>A (p.Val190Met)SNV Uncertain significance 473028 rs769400934 16:78420808-78420808 16:78386911-78386911
44 WWOX NM_016373.4(WWOX):c.673C>G (p.Leu225Val)SNV Uncertain significance 451480 rs376040091 16:78458834-78458834 16:78424937-78424937
45 WWOX NM_016373.4(WWOX):c.1114G>T (p.Gly372Ter)SNV Uncertain significance 450593 rs587777127 16:79245562-79245562 16:79211665-79211665
46 WWOX NM_016373.4(WWOX):c.1204G>A (p.Glu402Lys)SNV Uncertain significance 449787 rs200839945 16:79245652-79245652 16:79211755-79211755
47 WWOX NM_016373.4(WWOX):c.1240G>A (p.Gly414Ser)SNV Uncertain significance 449677 rs201606637 16:79245688-79245688 16:79211791-79211791
48 WWOX NM_016373.4(WWOX):c.937C>G (p.Pro313Ala)SNV Uncertain significance 410083 rs370345936 16:78466530-78466530 16:78432633-78432633
49 WWOX NM_016373.4(WWOX):c.943G>A (p.Gly315Arg)SNV Uncertain significance 410091 rs768172617 16:78466536-78466536 16:78432639-78432639
50 WWOX NM_016373.4(WWOX):c.958G>A (p.Ala320Thr)SNV Uncertain significance 410085 rs368670215 16:78466551-78466551 16:78432654-78432654

UniProtKB/Swiss-Prot genetic disease variations for Spinocerebellar Ataxia, Autosomal Recessive 12:

73
# Symbol AA change Variation ID SNP ID
1 WWOX p.Pro47Thr VAR_070992 rs587777128
2 WWOX p.Gly372Arg VAR_070993 rs587777127

Expression for Spinocerebellar Ataxia, Autosomal Recessive 12

Search GEO for disease gene expression data for Spinocerebellar Ataxia, Autosomal Recessive 12.

Pathways for Spinocerebellar Ataxia, Autosomal Recessive 12

GO Terms for Spinocerebellar Ataxia, Autosomal Recessive 12

Sources for Spinocerebellar Ataxia, Autosomal Recessive 12

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