MCID: VSC016
MIFTS: 41

Vasculopathy, Retinal, with Cerebral Leukodystrophy

Categories: Genetic diseases, Rare diseases, Nephrological diseases, Cardiovascular diseases

Aliases & Classifications for Vasculopathy, Retinal, with Cerebral Leukodystrophy

MalaCards integrated aliases for Vasculopathy, Retinal, with Cerebral Leukodystrophy:

Name: Vasculopathy, Retinal, with Cerebral Leukodystrophy 57 75 29 13 6 40 73
Rvcl 57 53 75
Crv 57 53 75
Retinopathy, Vascular, with Cerebral and Renal Involvement and Raynaud and Migraine Phenomena 57 53
Retinal Vasculopathy with Cerebral Leukodystrophy 53 37
Cerebroretinal Vasculopathy, Hereditary 57 53
Vascular Retinopathy with Cerebral and Renal Involvement and Raynaud and Migraine Phenomena 75
Retinal Vasculopathy with Cerebral Leukoencephalopathy and Systemic Manifestations 53
Autosomal Dominant Retinal Vasculopathy with Cerebral Leukodystrophy 53
Hereditary Endotheliopathy with Retinopathy-Nephropathy-Stroke 75
Retinal Vasculopathy and Cerebral Leukoencephalopathy 53
Cerebroretinal Vasculopathy, Hereditary; Crv 57
Cerebroretinal Vasculopathy 75
Rvcl-S 53
Adrvcl 53
Herns 75

Characteristics:

OMIM:

57
Inheritance:
autosomal dominant

Miscellaneous:
progressive disorder
onset in adulthood
death occurs 5 to 10 years after onset


HPO:

32
vasculopathy, retinal, with cerebral leukodystrophy:
Onset and clinical course adult onset progressive
Inheritance autosomal dominant inheritance


Classifications:



Summaries for Vasculopathy, Retinal, with Cerebral Leukodystrophy

NIH Rare Diseases : 53 Retinal vasculopathy with cerebral leukodystrophy (RVCL) is a rare, genetic condition that primarily affects the central nervous system. Symptoms begin in adulthood (usually in the 40s) and may include loss of vision, mini-strokes, and dementia. Death can sometimes occur within 10 years of the first symptoms appearing. RVCL is inherited in an autosomal dominant manner and is caused by mutations in the TREX1 gene. Treatments currently aim to manage or alleviate the symptoms rather than treating the underlying cause.RVCL is now considered to include the following 3 conditions which were previously thought to be distinct: hereditary endotheliopathy, retinopathy, nephropathy, and stroke (HERNS); cerebroretinal vasculopathy (CRV); and hereditary vascular retinopathy (HVR).

MalaCards based summary : Vasculopathy, Retinal, with Cerebral Leukodystrophy, also known as rvcl, is related to hereditary endotheliopathy, retinopathy, nephropathy, and stroke and leukodystrophy, and has symptoms including hemiparesis and seizures. An important gene associated with Vasculopathy, Retinal, with Cerebral Leukodystrophy is TREX1 (Three Prime Repair Exonuclease 1), and among its related pathways/superpathways are Cytosolic DNA-sensing pathway and Chks in Checkpoint Regulation. The drugs Aclarubicin and Aclacinomycins have been mentioned in the context of this disorder. Affiliated tissues include brain, retina and skin, and related phenotypes are seizures and dysarthria

OMIM : 57 Retinal vasculopathy with cerebral leukodystrophy is an adult-onset autosomal dominant disorder involving the microvessels of the brain and resulting in central nervous system degeneration with progressive loss of vision, stroke, motor impairment, and cognitive decline. Death occurs in most patients 5 to 10 years after onset. A subset of affected individuals have systemic vascular involvement evidenced by Raynaud's phenomenon, micronodular cirrhosis, and glomerular dysfunction (summary by Richards et al., 2007). (192315)

UniProtKB/Swiss-Prot : 75 Vasculopathy, retinal, with cerebral leukodystrophy: A microvascular endotheliopathy resulting in central nervous system degeneration and retinopathy, with progressive loss of vision, stroke, motor impairment, and cognitive decline. The ocular manifestations are characterized by telangiectasias, microaneurysms and retinal capillary obliteration starting in the macula. Diseased cerebral white matter has prominent small infarcts that often coalesce to pseudotumors.

Wikipedia : 76 Autosomal Dominant Retinal Vasculopathy with Cerebral Leukodystrophy (AD-RVCL) (previously known also as... more...

Related Diseases for Vasculopathy, Retinal, with Cerebral Leukodystrophy

Diseases related to Vasculopathy, Retinal, with Cerebral Leukodystrophy via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 hereditary endotheliopathy, retinopathy, nephropathy, and stroke 11.3
2 leukodystrophy 10.3
3 cerebritis 10.3
4 retinitis 10.3
5 aicardi-goutieres syndrome 1 9.2 SHISA5 TREX1
6 aicardi-goutieres syndrome 8.5 ATRIP SHISA5 TREX1

Graphical network of the top 20 diseases related to Vasculopathy, Retinal, with Cerebral Leukodystrophy:



Diseases related to Vasculopathy, Retinal, with Cerebral Leukodystrophy

Symptoms & Phenotypes for Vasculopathy, Retinal, with Cerebral Leukodystrophy

Symptoms via clinical synopsis from OMIM:

57
Neurologic Central Nervous System:
seizures
dysarthria
migraine
apraxia
stroke
more
Head And Neck Eyes:
retinal hemorrhage
macular edema
retinal exudates
retinal vasculopathy
decreased visual acuity, progressive
more
Abdomen Liver:
micronodular cirrhosis (less common)

Skin Nails Hair Skin:
punctate vasculitis skin lesions

Laboratory Abnormalities:
proteinuria
hematuria
abnormal liver enzymes

Cardiovascular Vascular:
raynaud phenomenon

Genitourinary Kidneys:
glomerular dysfunction (variable)

Neurologic Behavioral Psychiatric Manifestations:
psychiatric disturbances


Clinical features from OMIM:

192315

Human phenotypes related to Vasculopathy, Retinal, with Cerebral Leukodystrophy:

32 (show all 27)
# Description HPO Frequency HPO Source Accession
1 seizures 32 HP:0001250
2 dysarthria 32 HP:0001260
3 behavioral abnormality 32 HP:0000708
4 visual impairment 32 HP:0000505
5 proteinuria 32 HP:0000093
6 progressive visual loss 32 HP:0000529
7 elevated hepatic transaminases 32 HP:0002910
8 migraine 32 HP:0002076
9 hematuria 32 HP:0000790
10 apraxia 32 HP:0002186
11 dementia 32 HP:0000726
12 stroke 32 HP:0001297
13 central nervous system degeneration 32 HP:0007009
14 retinal hemorrhage 32 HP:0000573
15 hemiparesis 32 HP:0001269
16 abnormality of the periventricular white matter 32 HP:0002518
17 elevated erythrocyte sedimentation rate 32 HP:0003565
18 raynaud phenomenon 32 HP:0030880
19 telangiectasia 32 HP:0001009
20 lower limb hyperreflexia 32 HP:0002395
21 retinal exudate 32 HP:0001147
22 macular edema 32 HP:0040049
23 progressive forgetfulness 32 HP:0007017
24 vasculitis in the skin 32 HP:0200029
25 limb pain 32 HP:0009763
26 micronodular cirrhosis 32 occasional (7.5%) HP:0001413
27 punctate vasculitis skin lesions 32 HP:0200030

UMLS symptoms related to Vasculopathy, Retinal, with Cerebral Leukodystrophy:


hemiparesis, seizures

Drugs & Therapeutics for Vasculopathy, Retinal, with Cerebral Leukodystrophy

Drugs for Vasculopathy, Retinal, with Cerebral Leukodystrophy (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 6)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Aclarubicin Investigational Phase 1 57576-44-0 451415
2 Aclacinomycins Phase 1
3 Adjuvants, Immunologic Phase 1
4 Anti-Bacterial Agents Phase 1
5 Antibiotics, Antitubercular Phase 1
6 Topoisomerase Inhibitors Phase 1

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Aclarubicin for the Treatment of Retinal Vasculopathy With Cerebral Leukodystrophy Recruiting NCT02723448 Phase 1 aclarubicin

Search NIH Clinical Center for Vasculopathy, Retinal, with Cerebral Leukodystrophy

Genetic Tests for Vasculopathy, Retinal, with Cerebral Leukodystrophy

Genetic tests related to Vasculopathy, Retinal, with Cerebral Leukodystrophy:

# Genetic test Affiliating Genes
1 Vasculopathy, Retinal, with Cerebral Leukodystrophy 29 TREX1

Anatomical Context for Vasculopathy, Retinal, with Cerebral Leukodystrophy

MalaCards organs/tissues related to Vasculopathy, Retinal, with Cerebral Leukodystrophy:

41
Brain, Retina, Skin, Liver

Publications for Vasculopathy, Retinal, with Cerebral Leukodystrophy

Articles related to Vasculopathy, Retinal, with Cerebral Leukodystrophy:

# Title Authors Year
1
Phenotypic Variability in a Mexican Mestizo Family with Retinal Vasculopathy with Cerebral Leukodystrophy and TREX1 Mutation p.V235Gfs*6. ( 29718010 )
2018
2
Renal histopathological findings of retinal vasculopathy with cerebral leukodystrophy. ( 29322432 )
2018
3
Sporadic case of retinal vasculopathy with cerebral leukodystrophy/hereditary endotheliopathy retinopathy nephropathy stroke with novel TREX1 mutation. ( 27773153 )
2016
4
TREX1 C-terminal frameshift mutations in the systemic variant of retinal vasculopathy with cerebral leukodystrophy. ( 25213617 )
2014
5
Novel ophthalmic pathology in an autopsy case of autosomal dominant retinal vasculopathy with cerebral leukodystrophy. ( 21131853 )
2011
6
C-terminal truncations in human 3'-5' DNA exonuclease TREX1 cause autosomal dominant retinal vasculopathy with cerebral leukodystrophy. ( 17660820 )
2007

Variations for Vasculopathy, Retinal, with Cerebral Leukodystrophy

ClinVar genetic disease variations for Vasculopathy, Retinal, with Cerebral Leukodystrophy:

6
(show top 50) (show all 58)
# Gene Variation Type Significance SNP ID Assembly Location
1 TREX1 NM_033629.4(TREX1): c.341G> A (p.Arg114His) single nucleotide variant risk factor rs72556554 GRCh37 Chromosome 3, 48508395: 48508395
2 TREX1 NM_033629.4(TREX1): c.341G> A (p.Arg114His) single nucleotide variant risk factor rs72556554 GRCh38 Chromosome 3, 48466996: 48466996
3 TREX1 TREX1, 1-BP INS, 3688G insertion Pathogenic
4 TREX1 TREX1, 4-BP DUP, 3727GTCA duplication Pathogenic
5 TREX1 NM_033629.4(TREX1): c.912G> A (p.Leu304=) single nucleotide variant Benign rs3135945 GRCh38 Chromosome 3, 48467567: 48467567
6 TREX1 NM_033629.4(TREX1): c.912G> A (p.Leu304=) single nucleotide variant Benign rs3135945 GRCh37 Chromosome 3, 48508966: 48508966
7 TREX1 NM_033629.4(TREX1): c.-515T> C single nucleotide variant Likely benign rs148393533 GRCh38 Chromosome 3, 48465821: 48465821
8 TREX1 NM_033629.4(TREX1): c.-515T> C single nucleotide variant Likely benign rs148393533 GRCh37 Chromosome 3, 48507220: 48507220
9 TREX1 NM_033629.4(TREX1): c.-510delC deletion Likely benign rs886058621 GRCh38 Chromosome 3, 48465826: 48465826
10 TREX1 NM_033629.4(TREX1): c.-510delC deletion Likely benign rs886058621 GRCh37 Chromosome 3, 48507225: 48507225
11 TREX1 NM_033629.4(TREX1): c.-100C> T single nucleotide variant Uncertain significance rs886058623 GRCh38 Chromosome 3, 48466236: 48466236
12 TREX1 NM_033629.4(TREX1): c.-100C> T single nucleotide variant Uncertain significance rs886058623 GRCh37 Chromosome 3, 48507635: 48507635
13 TREX1 NM_033629.4(TREX1): c.-60C> T single nucleotide variant Likely benign rs2279076 GRCh38 Chromosome 3, 48466276: 48466276
14 TREX1 NM_033629.4(TREX1): c.-60C> T single nucleotide variant Likely benign rs2279076 GRCh37 Chromosome 3, 48507675: 48507675
15 TREX1 NM_033629.4(TREX1): c.9G> A (p.Ser3=) single nucleotide variant Uncertain significance rs762687506 GRCh38 Chromosome 3, 48466664: 48466664
16 TREX1 NM_033629.4(TREX1): c.9G> A (p.Ser3=) single nucleotide variant Uncertain significance rs762687506 GRCh37 Chromosome 3, 48508063: 48508063
17 TREX1 NM_033629.4(TREX1): c.198G> A (p.Lys66=) single nucleotide variant Benign/Likely benign rs3135943 GRCh38 Chromosome 3, 48466853: 48466853
18 TREX1 NM_033629.4(TREX1): c.198G> A (p.Lys66=) single nucleotide variant Benign/Likely benign rs3135943 GRCh37 Chromosome 3, 48508252: 48508252
19 TREX1 NM_033629.4(TREX1): c.418A> G (p.Met140Val) single nucleotide variant Uncertain significance rs761526437 GRCh38 Chromosome 3, 48467073: 48467073
20 TREX1 NM_033629.4(TREX1): c.418A> G (p.Met140Val) single nucleotide variant Uncertain significance rs761526437 GRCh37 Chromosome 3, 48508472: 48508472
21 TREX1 NM_033629.4(TREX1): c.-199A> G single nucleotide variant Uncertain significance rs767364235 GRCh38 Chromosome 3, 48466137: 48466137
22 TREX1 NM_033629.4(TREX1): c.-199A> G single nucleotide variant Uncertain significance rs767364235 GRCh37 Chromosome 3, 48507536: 48507536
23 TREX1 NM_033629.4(TREX1): c.-68T> C single nucleotide variant Benign rs3135941 GRCh38 Chromosome 3, 48466268: 48466268
24 TREX1 NM_033629.4(TREX1): c.-68T> C single nucleotide variant Benign rs3135941 GRCh37 Chromosome 3, 48507667: 48507667
25 TREX1 NM_033629.5(TREX1): c.183G> A (p.Pro61=) single nucleotide variant Likely benign rs55852466 GRCh38 Chromosome 3, 48466838: 48466838
26 TREX1 NM_033629.5(TREX1): c.183G> A (p.Pro61=) single nucleotide variant Likely benign rs55852466 GRCh37 Chromosome 3, 48508237: 48508237
27 TREX1 NM_033629.4(TREX1): c.312G> C (p.Leu104=) single nucleotide variant Uncertain significance rs56162833 GRCh38 Chromosome 3, 48466967: 48466967
28 TREX1 NM_033629.4(TREX1): c.312G> C (p.Leu104=) single nucleotide variant Uncertain significance rs56162833 GRCh37 Chromosome 3, 48508366: 48508366
29 TREX1 NM_033629.4(TREX1): c.*37T> C single nucleotide variant Benign rs3135946 GRCh38 Chromosome 3, 48467637: 48467637
30 TREX1 NM_033629.4(TREX1): c.*37T> C single nucleotide variant Benign rs3135946 GRCh37 Chromosome 3, 48509036: 48509036
31 TREX1 NM_033629.4(TREX1): c.-127G> C single nucleotide variant Uncertain significance rs577465983 GRCh38 Chromosome 3, 48466209: 48466209
32 TREX1 NM_033629.4(TREX1): c.-127G> C single nucleotide variant Uncertain significance rs577465983 GRCh37 Chromosome 3, 48507608: 48507608
33 TREX1 NM_033629.4(TREX1): c.394C> G (p.Pro132Ala) single nucleotide variant Likely benign rs200510205 GRCh38 Chromosome 3, 48467049: 48467049
34 TREX1 NM_033629.4(TREX1): c.394C> G (p.Pro132Ala) single nucleotide variant Likely benign rs200510205 GRCh37 Chromosome 3, 48508448: 48508448
35 TREX1 NM_033629.4(TREX1): c.462T> C (p.Asp154=) single nucleotide variant Benign/Likely benign rs3135944 GRCh38 Chromosome 3, 48467117: 48467117
36 TREX1 NM_033629.4(TREX1): c.462T> C (p.Asp154=) single nucleotide variant Benign/Likely benign rs3135944 GRCh37 Chromosome 3, 48508516: 48508516
37 TREX1 NM_033629.4(TREX1): c.536T> C (p.Leu179Pro) single nucleotide variant Uncertain significance rs886058625 GRCh38 Chromosome 3, 48467191: 48467191
38 TREX1 NM_033629.4(TREX1): c.536T> C (p.Leu179Pro) single nucleotide variant Uncertain significance rs886058625 GRCh37 Chromosome 3, 48508590: 48508590
39 TREX1 NM_033629.4(TREX1): c.-287C> T single nucleotide variant Uncertain significance rs377157141 GRCh38 Chromosome 3, 48466049: 48466049
40 TREX1 NM_033629.4(TREX1): c.-287C> T single nucleotide variant Uncertain significance rs377157141 GRCh37 Chromosome 3, 48507448: 48507448
41 TREX1 NM_033629.4(TREX1): c.-206G> T single nucleotide variant Uncertain significance rs886058622 GRCh38 Chromosome 3, 48466130: 48466130
42 TREX1 NM_033629.4(TREX1): c.-206G> T single nucleotide variant Uncertain significance rs886058622 GRCh37 Chromosome 3, 48507529: 48507529
43 TREX1 NM_033629.4(TREX1): c.-117C> T single nucleotide variant Likely benign rs548710061 GRCh38 Chromosome 3, 48466219: 48466219
44 TREX1 NM_033629.4(TREX1): c.-117C> T single nucleotide variant Likely benign rs548710061 GRCh37 Chromosome 3, 48507618: 48507618
45 TREX1 NM_033629.4(TREX1): c.-34_-31delCTGC deletion Uncertain significance rs886058624 GRCh38 Chromosome 3, 48466302: 48466305
46 TREX1 NM_033629.4(TREX1): c.-34_-31delCTGC deletion Uncertain significance rs886058624 GRCh37 Chromosome 3, 48507701: 48507704
47 TREX1 NM_033629.4(TREX1): c.531T> C (p.Tyr177=) single nucleotide variant Benign rs11797 GRCh37 Chromosome 3, 48508585: 48508585
48 TREX1 NM_033629.4(TREX1): c.531T> C (p.Tyr177=) single nucleotide variant Benign rs11797 GRCh38 Chromosome 3, 48467186: 48467186
49 TREX1 NM_033629.4(TREX1): c.899C> T (p.Ala300Val) single nucleotide variant Uncertain significance GRCh37 Chromosome 3, 48508953: 48508953
50 TREX1 NM_033629.4(TREX1): c.899C> T (p.Ala300Val) single nucleotide variant Uncertain significance GRCh38 Chromosome 3, 48467554: 48467554

Expression for Vasculopathy, Retinal, with Cerebral Leukodystrophy

Search GEO for disease gene expression data for Vasculopathy, Retinal, with Cerebral Leukodystrophy.

Pathways for Vasculopathy, Retinal, with Cerebral Leukodystrophy

Pathways related to Vasculopathy, Retinal, with Cerebral Leukodystrophy according to KEGG:

37
# Name Kegg Source Accession
1 Cytosolic DNA-sensing pathway hsa04623

Pathways related to Vasculopathy, Retinal, with Cerebral Leukodystrophy according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
11.56 ATRIP TREX1
2
Show member pathways
10.99 ATRIP SHISA5

GO Terms for Vasculopathy, Retinal, with Cerebral Leukodystrophy

Cellular components related to Vasculopathy, Retinal, with Cerebral Leukodystrophy according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 nuclear envelope GO:0005635 8.62 SHISA5 TREX1

Biological processes related to Vasculopathy, Retinal, with Cerebral Leukodystrophy according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 DNA repair GO:0006281 9.16 ATRIP TREX1
2 DNA replication GO:0006260 8.96 ATRIP TREX1
3 nucleic acid phosphodiester bond hydrolysis GO:0090305 8.62 ATRIP TREX1

Molecular functions related to Vasculopathy, Retinal, with Cerebral Leukodystrophy according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 exonuclease activity GO:0004527 8.62 ATRIP TREX1

Sources for Vasculopathy, Retinal, with Cerebral Leukodystrophy

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
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49 NCI
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54 NINDS
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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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