LKPAT
MCID: LKN017
MIFTS: 27

Leukoencephalopathy with Ataxia (LKPAT)

Categories: Eye diseases, Genetic diseases, Neuronal diseases
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Aliases & Classifications for Leukoencephalopathy with Ataxia

MalaCards integrated aliases for Leukoencephalopathy with Ataxia:

Name: Leukoencephalopathy with Ataxia 57 73 5 38 71
Lkpat 57 73

Characteristics:


Inheritance:

Autosomal recessive 57

OMIM®:

57 (Updated 08-Dec-2022)
Miscellaneous:
two peaks of onset, childhood and adult
variable clinical features


Classifications:



External Ids:

OMIM® 57 615651
UMLS 71 C3810242

Summaries for Leukoencephalopathy with Ataxia

OMIM®: 57 Leukoencephalopathy with ataxia is an autosomal recessive neurologic disorder with a characteristic pattern of white matter abnormalities on brain MRI. Affected individuals have prominent signal abnormalities and decreased apparent diffusion coefficient (ADC) values in the posterior limbs of the internal capsules, middle cerebral peduncles, pyramidal tracts in the pons, and middle cerebellar peduncles. The findings suggest myelin microvacuolation restricted to certain brain regions. Clinical features include ataxia and unstable gait; more variable abnormalities may include visual field defects, headaches, and learning disabilities (summary by Depienne et al., 2013). (615651) (Updated 08-Dec-2022)

MalaCards based summary: Leukoencephalopathy with Ataxia, also known as lkpat, is related to clcn2-related leukoencephalopathy and leukodystrophy, hypomyelinating, 7, with or without oligodontia and/or hypogonadotropic hypogonadism, and has symptoms including headache and gait ataxia. An important gene associated with Leukoencephalopathy with Ataxia is CLCN2 (Chloride Voltage-Gated Channel 2). Affiliated tissues include pons and brain, and related phenotypes are optic neuropathy and visual field defect

UniProtKB/Swiss-Prot: 73 An autosomal recessive neurologic disorder with a characteristic pattern of white matter abnormalities on brain MRI. Affected individuals have prominent signal abnormalities and decreased apparent diffusion coefficient values in the posterior limbs of the internal capsules, middle cerebral peduncles, pyramidal tracts in the pons, and middle cerebellar peduncles, suggesting myelin microvacuolation. Clinical features include ataxia and unstable gait. More variable abnormalities may include visual field defects, headaches, and learning disabilities.

Related Diseases for Leukoencephalopathy with Ataxia

Diseases related to Leukoencephalopathy with Ataxia via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 clcn2-related leukoencephalopathy 11.3
2 leukodystrophy, hypomyelinating, 7, with or without oligodontia and/or hypogonadotropic hypogonadism 9.9
3 tooth agenesis 9.9
4 visual epilepsy 9.9
5 vestibular nystagmus 9.9
6 pathologic nystagmus 9.9
7 polr3-related leukodystrophy 9.9

Graphical network of the top 20 diseases related to Leukoencephalopathy with Ataxia:



Diseases related to Leukoencephalopathy with Ataxia

Symptoms & Phenotypes for Leukoencephalopathy with Ataxia

Human phenotypes related to Leukoencephalopathy with Ataxia:

30 (show all 7)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 optic neuropathy 30 Occasional (7.5%) HP:0001138
2 visual field defect 30 Occasional (7.5%) HP:0001123
3 abnormal chorioretinal morphology 30 Occasional (7.5%) HP:0000532
4 headache 30 HP:0002315
5 gait ataxia 30 HP:0002066
6 leukoencephalopathy 30 HP:0002352
7 limb ataxia 30 HP:0002070

Symptoms via clinical synopsis from OMIM®:

57 (Updated 08-Dec-2022)
Neurologic Central Nervous System:
headache
gait ataxia
leukoencephalopathy
limb ataxia
learning disabilities (in some patients)
more
Head And Neck Eyes:
visual field defects (in some patients)
chorioretinopathy (in some patients)
optic neuropathy (in some patients)

Clinical features from OMIM®:

615651 (Updated 08-Dec-2022)

UMLS symptoms related to Leukoencephalopathy with Ataxia:


headache; gait ataxia

Drugs & Therapeutics for Leukoencephalopathy with Ataxia

Search Clinical Trials, NIH Clinical Center for Leukoencephalopathy with Ataxia

Genetic Tests for Leukoencephalopathy with Ataxia

Anatomical Context for Leukoencephalopathy with Ataxia

Organs/tissues related to Leukoencephalopathy with Ataxia:

MalaCards : Pons, Brain

Publications for Leukoencephalopathy with Ataxia

Articles related to Leukoencephalopathy with Ataxia:

(show all 11)
# Title Authors PMID Year
1
Brain white matter oedema due to ClC-2 chloride channel deficiency: an observational analytical study. 57 5
23707145 2013
2
Frequency spectrum of rare and clinically relevant markers in multiethnic Indian populations (ClinIndb): A resource for genomic medicine in India. 5
32906206 2020
3
Optimizing clinical exome design and parallel gene-testing for recessive genetic conditions in preconception carrier screening: Translational research genomic data from 14,125 exomes. 5
31589614 2019
4
Exome sequencing of ion channel genes reveals complex profiles confounding personal risk assessment in epilepsy. 5
21703448 2011
5
Leukoencephalopathy upon disruption of the chloride channel ClC-2. 57
17567819 2007
6
Mutations in CLCN2 encoding a voltage-gated chloride channel are associated with idiopathic generalized epilepsies. 5
12612585 2003
7
Male germ cells and photoreceptors, both dependent on close cell-cell interactions, degenerate upon ClC-2 Cl(-) channel disruption. 57
11250895 2001
8
Seizures and central vestibular nystagmus as the initial presentation of leukoencephalopathy with ataxia (LKPAT). 62
36301363 2022
9
A novel homozygous change of CLCN2 (p.His590Pro) is associated with a subclinical form of leukoencephalopathy with ataxia (LKPAT). 62
28473625 2017
10
Assessment of myelination in hypomyelinating disorders by quantitative MRI. 62
22911904 2012
11
Leukoencephalopathy with ataxia, hypodontia, and hypomyelination. 62
15851747 2005

Variations for Leukoencephalopathy with Ataxia

ClinVar genetic disease variations for Leukoencephalopathy with Ataxia:

5 (show all 42)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 CLCN2 NM_004366.6(CLCN2):c.1397-1G>A SNV Pathogenic
813301 rs1478304584 GRCh37: 3:184072447-184072447
GRCh38: 3:184354659-184354659
2 CLCN2 NM_004366.6(CLCN2):c.985_986del (p.Ile329fs) DEL Pathogenic
1032901 rs1245141384 GRCh37: 3:184074880-184074881
GRCh38: 3:184357092-184357093
3 CLCN2 NM_004366.6(CLCN2):c.828dup (p.Arg277fs) DUP Pathogenic
100632 rs587777112 GRCh37: 3:184075219-184075220
GRCh38: 3:184357431-184357432
4 CLCN2 NM_004366.6(CLCN2):c.668_672del (p.Leu223fs) DEL Pathogenic
1279936 GRCh37: 3:184075588-184075592
GRCh38: 3:184357800-184357804
5 CLCN2 NM_004366.6(CLCN2):c.1709G>A (p.Trp570Ter) SNV Pathogenic
100629 rs201330912 GRCh37: 3:184071901-184071901
GRCh38: 3:184354113-184354113
6 CLCN2 NM_004366.6(CLCN2):c.430_435del (p.Leu144_Ile145del) DEL Pathogenic
100630 rs587777110 GRCh37: 3:184076016-184076021
GRCh38: 3:184358228-184358233
7 CLCN2 NM_004366.6(CLCN2):c.1499C>T (p.Ala500Val) SNV Pathogenic
100631 rs587777111 GRCh37: 3:184072344-184072344
GRCh38: 3:184354556-184354556
8 CLCN2 NM_004366.6(CLCN2):c.597dup (p.Met200fs) DUP Likely Pathogenic
9035 rs515726131 GRCh37: 3:184075767-184075768
GRCh38: 3:184357979-184357980
9 CLCN2 NM_004366.6(CLCN2):c.221-14_221-4del DEL Uncertain Significance
9036 rs515726132 GRCh37: 3:184076605-184076615
GRCh38: 3:184358817-184358827
10 CLCN2 NM_004366.6(CLCN2):c.704G>A (p.Arg235Gln) SNV Uncertain Significance
Uncertain Significance
9038 rs71318369 GRCh37: 3:184075476-184075476
GRCh38: 3:184357688-184357688
11 CLCN2 NM_004366.6(CLCN2):c.218G>A (p.Arg73His) SNV Uncertain Significance
217770 rs144412275 GRCh37: 3:184076765-184076765
GRCh38: 3:184358977-184358977
12 CLCN2 NM_004366.6(CLCN2):c.2173C>T (p.Arg725Trp) SNV Benign
217779 rs114702742 GRCh37: 3:184070569-184070569
GRCh38: 3:184352781-184352781
13 CLCN2 NM_004366.6(CLCN2):c.1856-3C>T SNV Not Provided
217773 rs371193424 GRCh37: 3:184071213-184071213
GRCh38: 3:184353425-184353425
14 CLCN2 NM_004366.6(CLCN2):c.2063G>A (p.Arg688Gln) SNV Not Provided
217777 rs111656822 GRCh37: 3:184070901-184070901
GRCh38: 3:184353113-184353113
15 CLCN2 NM_004366.6(CLCN2):c.1930C>T (p.Arg644Cys) SNV Not Provided
217774 rs148545588 GRCh37: 3:184071136-184071136
GRCh38: 3:184353348-184353348
16 CLCN2 NM_004366.6(CLCN2):c.2279C>T (p.Ala760Val) SNV Not Provided
217782 rs781034991 GRCh37: 3:184070112-184070112
GRCh38: 3:184352324-184352324
17 CLCN2 NM_004366.6(CLCN2):c.292G>C (p.Gly98Arg) SNV Not Provided
217784 rs863225249 GRCh37: 3:184076530-184076530
GRCh38: 3:184358742-184358742
18 CLCN2 NM_004366.6(CLCN2):c.1795G>A (p.Asp599Asn) SNV Not Provided
217794 rs141242566 GRCh37: 3:184071510-184071510
GRCh38: 3:184353722-184353722
19 CLCN2 NM_004366.6(CLCN2):c.1015G>C (p.Val339Leu) SNV Not Provided
217786 rs532632165 GRCh37: 3:184074851-184074851
GRCh38: 3:184357063-184357063
20 CLCN2 NM_004366.6(CLCN2):c.596G>C (p.Gly199Ala) SNV Not Provided
217772 rs863225248 GRCh37: 3:184075769-184075769
GRCh38: 3:184357981-184357981
21 CLCN2 NM_004366.6(CLCN2):c.2154G>C (p.Glu718Asp) SNV Not Provided
217778 rs2228292 GRCh37: 3:184070588-184070588
GRCh38: 3:184352800-184352800
22 CLCN2 NM_004366.6(CLCN2):c.2386C>T (p.Gln796Ter) SNV Not Provided
217796 rs376823689 GRCh37: 3:184069830-184069830
GRCh38: 3:184352042-184352042
23 CLCN2 NM_004366.6(CLCN2):c.2003C>G (p.Thr668Ser) SNV Not Provided
217776 rs9820367 GRCh37: 3:184071063-184071063
GRCh38: 3:184353275-184353275
24 CLCN2 NM_004366.6(CLCN2):c.2273G>A (p.Ser758Asn) SNV Not Provided
217781 rs753380048 GRCh37: 3:184070118-184070118
GRCh38: 3:184352330-184352330
25 CLCN2 NM_004366.6(CLCN2):c.246C>G (p.Phe82Leu) SNV Not Provided
217771 rs140463309 GRCh37: 3:184076576-184076576
GRCh38: 3:184358788-184358788
26 CLCN2 NM_004366.6(CLCN2):c.143C>G (p.Pro48Arg) SNV Not Provided
217768 rs115661422 GRCh37: 3:184076840-184076840
GRCh38: 3:184359052-184359052
27 CLCN2 NM_004366.6(CLCN2):c.1397G>A (p.Gly466Glu) SNV Not Provided
217790 rs863225254 GRCh37: 3:184072446-184072446
GRCh38: 3:184354658-184354658
28 CLCN2 NM_004366.6(CLCN2):c.1730G>A (p.Arg577Gln) SNV Not Provided
9039 rs137852682 GRCh37: 3:184071575-184071575
GRCh38: 3:184353787-184353787
29 CLCN2 NM_004366.6(CLCN2):c.203G>A (p.Arg68His) SNV Not Provided
217769 rs61729156 GRCh37: 3:184076780-184076780
GRCh38: 3:184358992-184358992
30 CLCN2 NM_004366.6(CLCN2):c.925C>T (p.Arg309Ter) SNV Not Provided
217785 rs863225250 GRCh37: 3:184075028-184075028
GRCh38: 3:184357240-184357240
31 CLCN2 NM_004366.6(CLCN2):c.1507G>A (p.Gly503Arg) SNV Not Provided
217793 rs777105668 GRCh37: 3:184072336-184072336
GRCh38: 3:184354548-184354548
32 CLCN2 NM_004366.6(CLCN2):c.2144G>A (p.Gly715Glu) SNV Not Provided
9037 rs137852681 GRCh37: 3:184070598-184070598
GRCh38: 3:184352810-184352810
33 CLCN2 NM_004366.6(CLCN2):c.1957A>T (p.Arg653Ter) SNV Not Provided
217795 rs863225256 GRCh37: 3:184071109-184071109
GRCh38: 3:184353321-184353321
34 CLCN2 NM_004366.6(CLCN2):c.1937G>A (p.Arg646Gln) SNV Not Provided
217775 rs115961753 GRCh37: 3:184071129-184071129
GRCh38: 3:184353341-184353341
35 CLCN2 NM_004366.6(CLCN2):c.1412G>A (p.Arg471His) SNV Not Provided
217791 rs771507094 GRCh37: 3:184072431-184072431
GRCh38: 3:184354643-184354643
36 CLCN2 NM_004366.6(CLCN2):c.130G>A (p.Gly44Arg) SNV Not Provided
217767 rs863225247 GRCh37: 3:184076853-184076853
GRCh38: 3:184359065-184359065
37 CLCN2 NM_004366.6(CLCN2):c.1143del (p.Gly382fs) DEL Not Provided
217788 rs863225252 GRCh37: 3:184073509-184073509
GRCh38: 3:184355721-184355721
38 CLCN2 NM_004366.6(CLCN2):c.1304del (p.Leu435fs) DEL Not Provided
217789 rs863225253 GRCh37: 3:184073184-184073184
GRCh38: 3:184355396-184355396
39 CLCN2 NM_004366.6(CLCN2):c.1422_1423del (p.Glu475fs) DEL Not Provided
217792 rs863225255 GRCh37: 3:184072420-184072421
GRCh38: 3:184354632-184354633
40 CLCN2 NM_004366.6(CLCN2):c.1113delinsACTGCTCAT (p.Ser375fs) INDEL Not Provided
217787 rs863225251 GRCh37: 3:184073539-184073539
GRCh38: 3:184355751-184355751
41 CLCN2 NM_004366.6(CLCN2):c.64-1107_639del DEL Not Provided
217783 GRCh37: 3:184075621-184078026
GRCh38: 3:184357833-184360238
42 CLCN2 NM_004366.6(CLCN2):c.2240G>A (p.Arg747His) SNV Not Provided
217780 rs144164281 GRCh37: 3:184070262-184070262
GRCh38: 3:184352474-184352474

UniProtKB/Swiss-Prot genetic disease variations for Leukoencephalopathy with Ataxia:

73
# Symbol AA change Variation ID SNP ID
1 CLCN2 p.Ala500Val VAR_070977 rs587777111

Expression for Leukoencephalopathy with Ataxia

Search GEO for disease gene expression data for Leukoencephalopathy with Ataxia.

Pathways for Leukoencephalopathy with Ataxia

GO Terms for Leukoencephalopathy with Ataxia

Sources for Leukoencephalopathy with Ataxia

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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