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RVCL
MCID: VSC016
MIFTS: 42

Vasculopathy, Retinal, with Cerebral Leukodystrophy (RVCL)

Categories: Genetic diseases, Rare diseases
Genes Variations Tissues Related diseases Publications Pathways Symptoms & Phenotypes Drugs
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Aliases & Classifications for Vasculopathy, Retinal, with Cerebral Leukodystrophy

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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:

MalaCards categories:
Global: Genetic diseases Rare diseases
See all MalaCards categories (disease lists)


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Summaries for Vasculopathy, Retinal, with Cerebral Leukodystrophy

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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 gomez-lopez-hernandez syndrome, and has symptoms including seizures and hemiparesis. 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 ataxia

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...

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Related Diseases for Vasculopathy, Retinal, with Cerebral Leukodystrophy

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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 11.5
2 gomez-lopez-hernandez syndrome 11.1
3 leukodystrophy 10.5
4 multiple sclerosis 10.2
5 hereditary vascular retinopathy 10.2
6 cutaneous collagenous vasculopathy 10.1
7 cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy, type 1 10.1
8 aicardi-goutieres syndrome 1 9.8 TREX1 SHISA5
9 aicardi-goutieres syndrome 9.5 TREX1 SHISA5 ATRIP

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



Diseases related to Vasculopathy, Retinal, with Cerebral Leukodystrophy
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Symptoms & Phenotypes for Vasculopathy, Retinal, with Cerebral Leukodystrophy

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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 37)
# Description HPO Frequency HPO Source Accession
1 seizures 32 frequent (33%) HP:0001250
2 ataxia 32 occasional (7.5%) HP:0001251
3 dysarthria 32 frequent (33%) HP:0001260
4 behavioral abnormality 32 frequent (33%) HP:0000708
5 visual impairment 32 HP:0000505
6 proteinuria 32 occasional (7.5%) HP:0000093
7 nephropathy 32 occasional (7.5%) HP:0000112
8 retinopathy 32 frequent (33%) HP:0000488
9 progressive visual loss 32 frequent (33%) HP:0000529
10 migraine 32 frequent (33%) HP:0002076
11 glomerulopathy 32 occasional (7.5%) HP:0100820
12 abnormality of the retinal vasculature 32 frequent (33%) HP:0008046
13 hematuria 32 occasional (7.5%) HP:0000790
14 apraxia 32 frequent (33%) HP:0002186
15 dementia 32 HP:0000726
16 stroke 32 frequent (33%) HP:0001297
17 mental deterioration 32 frequent (33%) HP:0001268
18 central nervous system degeneration 32 HP:0007009
19 retinal hemorrhage 32 HP:0000573
20 leukodystrophy 32 hallmark (90%) HP:0002415
21 hemiparesis 32 frequent (33%) HP:0001269
22 abnormality of the periventricular white matter 32 HP:0002518
23 raynaud phenomenon 32 HP:0030880
24 sensory impairment 32 occasional (7.5%) HP:0003474
25 elevated erythrocyte sedimentation rate 32 HP:0003565
26 telangiectasia 32 HP:0001009
27 lower limb hyperreflexia 32 HP:0002395
28 focal white matter lesions 32 hallmark (90%) HP:0007042
29 retinal exudate 32 HP:0001147
30 macular edema 32 HP:0040049
31 progressive forgetfulness 32 HP:0007017
32 micronodular cirrhosis 32 occasional (7.5%) HP:0001413
33 vasculitis in the skin 32 HP:0200029
34 limb pain 32 HP:0009763
35 punctate vasculitis skin lesions 32 HP:0200030
36 elevated hepatic transaminase 32 HP:0002910
37 diminished ability to concentrate 32 HP:0031987

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


seizures, hemiparesis
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Drugs & Therapeutics for Vasculopathy, Retinal, with Cerebral Leukodystrophy

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

(show all 7)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Aclarubicin Investigational Phase 1 57576-44-0 451415
2 Aclacinomycins Phase 1
3 Antibiotics, Antitubercular Phase 1
4 Anti-Bacterial Agents Phase 1
5 Topoisomerase Inhibitors Phase 1
6 Adjuvants, Immunologic Phase 1
7 Immunologic Factors Phase 1

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Aclarubicin for the Treatment of Retinal Vasculopathy With Cerebral Leukodystrophy Active, not recruiting NCT02723448 Phase 1 aclarubicin

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

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Genetic Tests for Vasculopathy, Retinal, with Cerebral Leukodystrophy

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

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

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

41
Brain, Retina, Skin, Liver
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Publications for Vasculopathy, Retinal, with Cerebral Leukodystrophy

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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
RVCL-S and CADASIL display distinct impaired vascular function. ( 30076273 )
2018
4
Retinal vasculopathy with cerebral leukoencephalopathy (RVCL): A rare mimic of tumefactive MS. ( 30194247 )
2018
5
Tumefactive lesions in retinal vasculopathy with cerebral leucoencephalopathy and systemic manifestations (RVCL-S): a role for neuroinflammation? ( 28794152 )
2017
6
Sporadic case of retinal vasculopathy with cerebral leukodystrophy/hereditary endotheliopathy retinopathy nephropathy stroke with novel TREX1 mutation. ( 27773153 )
2016
7
Multiple sclerosis-like lesions and type I interferon signature in a patient with RVCL. ( 25566545 )
2015
8
TREX1 C-terminal frameshift mutations in the systemic variant of retinal vasculopathy with cerebral leukodystrophy. ( 25213617 )
2014
9
Novel ophthalmic pathology in an autopsy case of autosomal dominant retinal vasculopathy with cerebral leukodystrophy. ( 21131853 )
2011
10
C-terminal truncations in human 3'-5' DNA exonuclease TREX1 cause autosomal dominant retinal vasculopathy with cerebral leukodystrophy. ( 17660820 )
2007
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Variations for Vasculopathy, Retinal, with Cerebral Leukodystrophy

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

6 (show top 50) (show all 74)
# Gene Variation Type Significance SNP ID Assembly Location
1 TREX1 NM_033629.5(TREX1): c.341G> A (p.Arg114His) single nucleotide variant risk factor rs72556554 GRCh37 Chromosome 3, 48508395: 48508395
2 TREX1 NM_033629.5(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_033629.2(TREX1): c.531C> T (p.Tyr177=) single nucleotide variant Benign rs11797 GRCh37 Chromosome 3, 48508585: 48508585
6 TREX1 NM_033629.2(TREX1): c.531C> T (p.Tyr177=) single nucleotide variant Benign rs11797 GRCh38 Chromosome 3, 48467186: 48467186
7 TREX1 NM_033629.5(TREX1): c.797A> G (p.Glu266Gly) single nucleotide variant Conflicting interpretations of pathogenicity rs55999987 GRCh37 Chromosome 3, 48508851: 48508851
8 TREX1 NM_033629.5(TREX1): c.797A> G (p.Glu266Gly) single nucleotide variant Conflicting interpretations of pathogenicity rs55999987 GRCh38 Chromosome 3, 48467452: 48467452
9 TREX1 NM_033629.4(TREX1): c.907A> C (p.Thr303Pro) single nucleotide variant Uncertain significance rs76224909 GRCh37 Chromosome 3, 48508961: 48508961
10 TREX1 NM_033629.4(TREX1): c.907A> C (p.Thr303Pro) single nucleotide variant Uncertain significance rs76224909 GRCh38 Chromosome 3, 48467562: 48467562
11 TREX1 NM_033629.4(TREX1): c.912G> A (p.Leu304=) single nucleotide variant Benign rs3135945 GRCh38 Chromosome 3, 48467567: 48467567
12 TREX1 NM_033629.4(TREX1): c.912G> A (p.Leu304=) single nucleotide variant Benign rs3135945 GRCh37 Chromosome 3, 48508966: 48508966
13 TREX1 NM_033629.4(TREX1): c.-515T> C single nucleotide variant Likely benign rs148393533 GRCh38 Chromosome 3, 48465821: 48465821
14 TREX1 NM_033629.4(TREX1): c.-515T> C single nucleotide variant Likely benign rs148393533 GRCh37 Chromosome 3, 48507220: 48507220
15 TREX1 NM_033629.4(TREX1): c.-510delC deletion Likely benign rs886058621 GRCh38 Chromosome 3, 48465826: 48465826
16 TREX1 NM_033629.4(TREX1): c.-510delC deletion Likely benign rs886058621 GRCh37 Chromosome 3, 48507225: 48507225
17 TREX1 NM_033629.4(TREX1): c.-100C> T single nucleotide variant Uncertain significance rs886058623 GRCh38 Chromosome 3, 48466236: 48466236
18 TREX1 NM_033629.4(TREX1): c.-100C> T single nucleotide variant Uncertain significance rs886058623 GRCh37 Chromosome 3, 48507635: 48507635
19 TREX1 NM_033629.4(TREX1): c.-60C> T single nucleotide variant Likely benign rs2279076 GRCh38 Chromosome 3, 48466276: 48466276
20 TREX1 NM_033629.4(TREX1): c.-60C> T single nucleotide variant Likely benign rs2279076 GRCh37 Chromosome 3, 48507675: 48507675
21 TREX1 NM_033629.4(TREX1): c.9G> A (p.Ser3=) single nucleotide variant Uncertain significance rs762687506 GRCh38 Chromosome 3, 48466664: 48466664
22 TREX1 NM_033629.4(TREX1): c.9G> A (p.Ser3=) single nucleotide variant Uncertain significance rs762687506 GRCh37 Chromosome 3, 48508063: 48508063
23 TREX1 NM_033629.4(TREX1): c.198G> A (p.Lys66=) single nucleotide variant Benign/Likely benign rs3135943 GRCh38 Chromosome 3, 48466853: 48466853
24 TREX1 NM_033629.4(TREX1): c.198G> A (p.Lys66=) single nucleotide variant Benign/Likely benign rs3135943 GRCh37 Chromosome 3, 48508252: 48508252
25 TREX1 NM_033629.4(TREX1): c.418A> G (p.Met140Val) single nucleotide variant Uncertain significance rs761526437 GRCh38 Chromosome 3, 48467073: 48467073
26 TREX1 NM_033629.4(TREX1): c.418A> G (p.Met140Val) single nucleotide variant Uncertain significance rs761526437 GRCh37 Chromosome 3, 48508472: 48508472
27 TREX1 NM_033629.4(TREX1): c.-199A> G single nucleotide variant Uncertain significance rs767364235 GRCh38 Chromosome 3, 48466137: 48466137
28 TREX1 NM_033629.4(TREX1): c.-199A> G single nucleotide variant Uncertain significance rs767364235 GRCh37 Chromosome 3, 48507536: 48507536
29 TREX1 NM_033629.4(TREX1): c.-68T> C single nucleotide variant Benign rs3135941 GRCh38 Chromosome 3, 48466268: 48466268
30 TREX1 NM_033629.4(TREX1): c.-68T> C single nucleotide variant Benign rs3135941 GRCh37 Chromosome 3, 48507667: 48507667
31 TREX1 NM_033629.5(TREX1): c.183G> A (p.Pro61=) single nucleotide variant Likely benign rs55852466 GRCh38 Chromosome 3, 48466838: 48466838
32 TREX1 NM_033629.5(TREX1): c.183G> A (p.Pro61=) single nucleotide variant Likely benign rs55852466 GRCh37 Chromosome 3, 48508237: 48508237
33 TREX1 NM_033629.4(TREX1): c.312G> C (p.Leu104=) single nucleotide variant Uncertain significance rs56162833 GRCh38 Chromosome 3, 48466967: 48466967
34 TREX1 NM_033629.4(TREX1): c.312G> C (p.Leu104=) single nucleotide variant Uncertain significance rs56162833 GRCh37 Chromosome 3, 48508366: 48508366
35 TREX1 NM_033629.4(TREX1): c.*37T> C single nucleotide variant Benign rs3135946 GRCh38 Chromosome 3, 48467637: 48467637
36 TREX1 NM_033629.4(TREX1): c.*37T> C single nucleotide variant Benign rs3135946 GRCh37 Chromosome 3, 48509036: 48509036
37 TREX1 NM_033629.4(TREX1): c.-127G> C single nucleotide variant Uncertain significance rs577465983 GRCh38 Chromosome 3, 48466209: 48466209
38 TREX1 NM_033629.4(TREX1): c.-127G> C single nucleotide variant Uncertain significance rs577465983 GRCh37 Chromosome 3, 48507608: 48507608
39 TREX1 NM_033629.4(TREX1): c.394C> G (p.Pro132Ala) single nucleotide variant Likely benign rs200510205 GRCh38 Chromosome 3, 48467049: 48467049
40 TREX1 NM_033629.4(TREX1): c.394C> G (p.Pro132Ala) single nucleotide variant Likely benign rs200510205 GRCh37 Chromosome 3, 48508448: 48508448
41 TREX1 NM_033629.4(TREX1): c.462T> C (p.Asp154=) single nucleotide variant Benign/Likely benign rs3135944 GRCh38 Chromosome 3, 48467117: 48467117
42 TREX1 NM_033629.4(TREX1): c.462T> C (p.Asp154=) single nucleotide variant Benign/Likely benign rs3135944 GRCh37 Chromosome 3, 48508516: 48508516
43 TREX1 NM_033629.4(TREX1): c.536T> C (p.Leu179Pro) single nucleotide variant Uncertain significance rs886058625 GRCh38 Chromosome 3, 48467191: 48467191
44 TREX1 NM_033629.4(TREX1): c.536T> C (p.Leu179Pro) single nucleotide variant Uncertain significance rs886058625 GRCh37 Chromosome 3, 48508590: 48508590
45 TREX1 NM_033629.4(TREX1): c.-287C> T single nucleotide variant Uncertain significance rs377157141 GRCh38 Chromosome 3, 48466049: 48466049
46 TREX1 NM_033629.4(TREX1): c.-287C> T single nucleotide variant Uncertain significance rs377157141 GRCh37 Chromosome 3, 48507448: 48507448
47 TREX1 NM_033629.4(TREX1): c.-206G> T single nucleotide variant Uncertain significance rs886058622 GRCh38 Chromosome 3, 48466130: 48466130
48 TREX1 NM_033629.4(TREX1): c.-206G> T single nucleotide variant Uncertain significance rs886058622 GRCh37 Chromosome 3, 48507529: 48507529
49 TREX1 NM_033629.4(TREX1): c.-117C> T single nucleotide variant Likely benign rs548710061 GRCh38 Chromosome 3, 48466219: 48466219
50 TREX1 NM_033629.4(TREX1): c.-117C> T single nucleotide variant Likely benign rs548710061 GRCh37 Chromosome 3, 48507618: 48507618
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Expression for Vasculopathy, Retinal, with Cerebral Leukodystrophy

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

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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
Chks in Checkpoint Regulation 64
Show member pathways
 11.56 ATRIP TREX1
2
DNA Damage Response 1
Show member pathways
 10.99 ATRIP SHISA5
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GO Terms for Vasculopathy, Retinal, with Cerebral Leukodystrophy

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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
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Sources for Vasculopathy, Retinal, with Cerebral Leukodystrophy

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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
The MalaCards human disease database index: 1-9 A B C D E F G H I J K L M N O P Q R S T U V W X Y Z
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