LKENP
MCID: LKN018
MIFTS: 27

Leukoencephalopathy, Progressive, with Ovarian Failure (LKENP)

Categories: Genetic diseases, Neuronal diseases
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Aliases & Classifications for Leukoencephalopathy, Progressive, with Ovarian Failure

MalaCards integrated aliases for Leukoencephalopathy, Progressive, with Ovarian Failure:

Name: Leukoencephalopathy, Progressive, with Ovarian Failure 57 73 28 5 38 71
Lkenp 57 73

Characteristics:


Inheritance:

Autosomal recessive 57

OMIM®:

57 (Updated 08-Dec-2022)
Miscellaneous:
progressive disorder
onset usually in young adulthood
earlier onset may occur


HPO:

30
leukoencephalopathy, progressive, with ovarian failure:
Onset and clinical course progressive


Classifications:



Summaries for Leukoencephalopathy, Progressive, with Ovarian Failure

OMIM®: 57 Progressive leukoencephalopathy with ovarian failure is an autosomal recessive neurodegenerative disorder characterized by loss of motor and cognitive skills, usually with onset in young adulthood. Some patients may have a history of delayed motor development or learning difficulties in early childhood. Neurologic decline is severe, usually resulting in gait difficulties, ataxia, spasticity, and cognitive decline and dementia. Most patients lose speech and become wheelchair-bound or bedridden. Brain MRI shows progressive white matter signal abnormalities in the deep white matter. Affected females develop premature ovarian failure (summary by Dallabona et al., 2014). (615889) (Updated 08-Dec-2022)

MalaCards based summary: Leukoencephalopathy, Progressive, with Ovarian Failure, also known as lkenp, is related to combined oxidative phosphorylation deficiency 8 and hypomyelinating leukodystrophy, and has symptoms including ataxia, tremor and muscle spasticity. An important gene associated with Leukoencephalopathy, Progressive, with Ovarian Failure is AARS2 (Alanyl-TRNA Synthetase 2, Mitochondrial). Affiliated tissues include brain, and related phenotypes are cerebellar atrophy and spasticity

UniProtKB/Swiss-Prot: 73 An autosomal recessive neurodegenerative disorder characterized by childhood- to adulthood-onset of signs of neurologic deterioration consisting of ataxia, spasticity, and cognitive decline with features of frontal lobe dysfunction. Brain MRI shows leukoencephalopathy with striking involvement of deep white matter, and cerebellar atrophy. All female patients develop premature ovarian failure.

Related Diseases for Leukoencephalopathy, Progressive, with Ovarian Failure

Diseases related to Leukoencephalopathy, Progressive, with Ovarian Failure via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 combined oxidative phosphorylation deficiency 8 9.6 POLR1C AARS2
2 hypomyelinating leukodystrophy 9.6 POLR1C AARS2
3 leukodystrophy 9.5 POLR1C AARS2

Symptoms & Phenotypes for Leukoencephalopathy, Progressive, with Ovarian Failure

Human phenotypes related to Leukoencephalopathy, Progressive, with Ovarian Failure:

30 (show all 15)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 cerebellar atrophy 30 Occasional (7.5%) HP:0001272
2 spasticity 30 HP:0001257
3 nystagmus 30 HP:0000639
4 depression 30 HP:0000716
5 ataxia 30 HP:0001251
6 dysarthria 30 HP:0001260
7 tremor 30 HP:0001337
8 premature ovarian insufficiency 30 HP:0008209
9 dystonia 30 HP:0001332
10 dementia 30 HP:0000726
11 loss of speech 30 HP:0002371
12 periventricular leukomalacia 30 HP:0006970
13 apraxia 30 HP:0002186
14 neurodegeneration 30 HP:0002180
15 progressive leukoencephalopathy 30 HP:0006980

Symptoms via clinical synopsis from OMIM®:

57 (Updated 08-Dec-2022)
Neurologic Central Nervous System:
spasticity
ataxia
dysarthria
tremor
dystonia
more
Neurologic Behavioral Psychiatric Manifestations:
depression
behavioral abnormalities
executive dysfunction

Muscle Soft Tissue:
isolated mitochondrial complex iv deficiency seen on biopsy

Head And Neck Eyes:
nystagmus

Endocrine Features:
premature ovarian failure

Clinical features from OMIM®:

615889 (Updated 08-Dec-2022)

UMLS symptoms related to Leukoencephalopathy, Progressive, with Ovarian Failure:


ataxia; tremor; muscle spasticity

GenomeRNAi Phenotypes related to Leukoencephalopathy, Progressive, with Ovarian Failure according to GeneCards Suite gene sharing:

25
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Resistant to vaccinia virus (VACV-A4L) infection GR00351-A-1 8.62 AARS2 POLR1C

Drugs & Therapeutics for Leukoencephalopathy, Progressive, with Ovarian Failure

Search Clinical Trials, NIH Clinical Center for Leukoencephalopathy, Progressive, with Ovarian Failure

Genetic Tests for Leukoencephalopathy, Progressive, with Ovarian Failure

Genetic tests related to Leukoencephalopathy, Progressive, with Ovarian Failure:

# Genetic test Affiliating Genes
1 Leukoencephalopathy, Progressive, with Ovarian Failure 28 AARS2

Anatomical Context for Leukoencephalopathy, Progressive, with Ovarian Failure

Organs/tissues related to Leukoencephalopathy, Progressive, with Ovarian Failure:

MalaCards : Brain

Publications for Leukoencephalopathy, Progressive, with Ovarian Failure

Articles related to Leukoencephalopathy, Progressive, with Ovarian Failure:

# Title Authors PMID Year
1
Novel (ovario) leukodystrophy related to AARS2 mutations. 57 5
24808023 2014
2
AARS2-Related Leukodystrophy: a Case Report and Literature Review. 5
35084689 2022
3
Use of whole-exome sequencing to determine the genetic basis of multiple mitochondrial respiratory chain complex deficiencies. 5
25058219 2014
4
The Primary Microglial Leukodystrophies: A Review. 62
35683020 2022

Variations for Leukoencephalopathy, Progressive, with Ovarian Failure

ClinVar genetic disease variations for Leukoencephalopathy, Progressive, with Ovarian Failure:

5 (show all 22)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 POLR1C, AARS2 NM_020745.4(AARS2):c.149T>G (p.Phe50Cys) SNV Pathogenic
143045 rs587777590 GRCh37: 6:44280912-44280912
GRCh38: 6:44313175-44313175
2 POLR1C, AARS2 NM_020745.4(AARS2):c.1561C>T (p.Arg521Ter) SNV Pathogenic
143046 rs587777591 GRCh37: 6:44272809-44272809
GRCh38: 6:44305072-44305072
3 POLR1C, AARS2 NM_020745.4(AARS2):c.2893G>A (p.Gly965Arg) SNV Pathogenic
143047 rs543267101 GRCh37: 6:44268349-44268349
GRCh38: 6:44300612-44300612
4 POLR1C, AARS2 NM_020745.4(AARS2):c.1213G>A (p.Glu405Lys) SNV Pathogenic
143048 rs587777592 GRCh37: 6:44274104-44274104
GRCh38: 6:44306367-44306367
5 POLR1C, AARS2 NM_020745.4(AARS2):c.1871G>A (p.Trp624Ter) SNV Pathogenic
982774 rs749701451 GRCh37: 6:44272054-44272054
GRCh38: 6:44304317-44304317
6 POLR1C, AARS2 NM_020745.4(AARS2):c.595C>T (p.Arg199Cys) SNV Pathogenic
213963 rs200105202 GRCh37: 6:44278885-44278885
GRCh38: 6:44311148-44311148
7 POLR1C, AARS2 NM_020745.4(AARS2):c.87_88dup (p.Leu30fs) DUP Pathogenic
1699307 GRCh37: 6:44280972-44280973
GRCh38: 6:44313235-44313236
8 POLR1C, AARS2 NM_020745.4(AARS2):c.1695C>G (p.Tyr565Ter) SNV Likely Pathogenic
1707535 GRCh37: 6:44272439-44272439
GRCh38: 6:44304702-44304702
9 POLR1C, AARS2 NM_020745.4(AARS2):c.781del (p.Gln261fs) DEL Likely Pathogenic
545896 rs1554148927 GRCh37: 6:44278149-44278149
GRCh38: 6:44310412-44310412
10 POLR1C, AARS2 NM_020745.4(AARS2):c.446G>A (p.Cys149Tyr) SNV Likely Pathogenic
1027410 GRCh37: 6:44279262-44279262
GRCh38: 6:44311525-44311525
11 POLR1C, AARS2 NM_020745.4(AARS2):c.385A>C (p.Thr129Pro) SNV Likely Pathogenic
1027411 GRCh37: 6:44279859-44279859
GRCh38: 6:44312122-44312122
12 POLR1C, AARS2 NM_020745.4(AARS2):c.907C>A (p.Pro303Thr) SNV Uncertain Significance
1708963 GRCh37: 6:44275119-44275119
GRCh38: 6:44307382-44307382
13 POLR1C, AARS2 NM_020745.4(AARS2):c.1687A>T (p.Asn563Tyr) SNV Uncertain Significance
1699302 GRCh37: 6:44272447-44272447
GRCh38: 6:44304710-44304710
14 POLR1C, AARS2 NM_020745.4(AARS2):c.2598+117G>C SNV Benign
1185349 GRCh37: 6:44269680-44269680
GRCh38: 6:44301943-44301943
15 POLR1C, AARS2 NM_020745.4(AARS2):c.2255+35C>A SNV Benign
1185350 GRCh37: 6:44270768-44270768
GRCh38: 6:44303031-44303031
16 POLR1C, AARS2 NM_020745.4(AARS2):c.1041-29A>G SNV Benign
1185351 GRCh37: 6:44274797-44274797
GRCh38: 6:44307060-44307060
17 POLR1C, AARS2 NM_020745.4(AARS2):c.2793+86_2793+87insCAGA INSERT Benign
1185550 GRCh37: 6:44268806-44268807
GRCh38: 6:44301069-44301070
18 POLR1C, AARS2 NM_020745.4(AARS2):c.2683-20A>G SNV Benign
1168141 GRCh37: 6:44269023-44269023
GRCh38: 6:44301286-44301286
19 POLR1C, AARS2 NM_020745.4(AARS2):c.2607G>A (p.Lys869=) SNV Benign
357059 rs498512 GRCh37: 6:44269193-44269193
GRCh38: 6:44301456-44301456
20 POLR1C, AARS2 NM_020745.4(AARS2):c.1015A>G (p.Ile339Val) SNV Benign
1164206 GRCh37: 6:44275011-44275011
GRCh38: 6:44307274-44307274
21 POLR1C, AARS2 NM_020745.4(AARS2):c.243+6G>A SNV Benign
357082 rs167772 GRCh37: 6:44280812-44280812
GRCh38: 6:44313075-44313075
22 POLR1C, AARS2 NM_020745.4(AARS2):c.2871A>G (p.Ser957=) SNV Benign
357055 rs325008 GRCh37: 6:44268371-44268371
GRCh38: 6:44300634-44300634

UniProtKB/Swiss-Prot genetic disease variations for Leukoencephalopathy, Progressive, with Ovarian Failure:

73
# Symbol AA change Variation ID SNP ID
1 AARS2 p.Phe50Cys VAR_071837 rs587777590
2 AARS2 p.Glu405Lys VAR_071841 rs587777592
3 AARS2 p.Gly965Arg VAR_071843 rs543267101

Expression for Leukoencephalopathy, Progressive, with Ovarian Failure

Search GEO for disease gene expression data for Leukoencephalopathy, Progressive, with Ovarian Failure.

Pathways for Leukoencephalopathy, Progressive, with Ovarian Failure

GO Terms for Leukoencephalopathy, Progressive, with Ovarian Failure

Sources for Leukoencephalopathy, Progressive, with Ovarian Failure

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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