eRAM

encyclopedia of Rare Disease Annotation for Precision Medicine

HOME
QUERY
- DISEASE
- GENOTYPE
NETWORK
- PHENOTYPE
- GENE
- COMMON
- DISEASE PAIR
DOWNLOAD
SUBMIT CASE
HELP&FAQ
- HELP&FAQ
- CONTACT US


	cadasil

Disease ID	436
Disease	cadasil
Definition	A hereditary cerebrovascular disorder caused by mutations in the Notch 3 gene. It is characterized by alterations of the muscular wall of the small vessels in the brain, resulting in transient ischemic attacks. It may lead to cognitive problems and dementia.
Synonym	cadasil [disease/finding] cadasil syndrome cadasil1 casil cerebral arteriopathy with subcortical infarcts and leukoencephalopathy cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy, type 1 cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (disorder) dementia, hereditary multi infarct type dementia, hereditary multi-infarct type
Orphanet	ORPHANET:136
OMIM	OMIM:125310
DOID	DOID:13945
UMLS	C0751587
MeSH	D046589
SNOMED-CT	SNOMEDCT_US_2016_09_01:390936003
Comorbidity	UMLS \| Disease \| Sentences' Count(Total Sentences:10) C0020538 \| hypertension \| 3 C0497327 \| dementia \| 3 C0149931 \| migraine \| 2 C0852949 \| arteriopathy \| 2 C0005586 \| bipolar disorder \| 1 C0011269 \| vascular dementia \| 1 C0679466 \| cognitive deficits \| 1 C0002395 \| alzheimer's disease \| 1 C0010068 \| coronary artery disease \| 1 C0002395 \| alzheimer disease \| 1
Curated Gene	Entrez_id \| Symbol \| Resource(Total Genes:1) 4854 \| NOTCH3 \| CTD_human;GHR;ORPHANET;UNIPROT
Inferring Gene	Entrez_id \| Symbol \| Resource(Total Genes:1) 4854 \| NOTCH3 \| CIPHER;CTD_human
Text Mined Gene	Entrez_id \| Symbol \| Score \| Resource(Total Genes:35) 477 \| ATP1A2 \| 2.256 \| DISEASES 773 \| CACNA1A \| 2.084 \| DISEASES 1282 \| COL4A1 \| 3.773 \| DISEASES 1453 \| CSNK1D \| 1.11 \| DISEASES 1471 \| CST3 \| 1.211 \| DISEASES 23741 \| EID1 \| 1.452 \| DISEASES 54821 \| ERCC6L \| 1.536 \| DISEASES 2104 \| ESRRG \| 1.117 \| DISEASES 2200 \| FBN1 \| 1.944 \| DISEASES 11146 \| GLMN \| 1.802 \| DISEASES 84667 \| HES7 \| 1.931 \| DISEASES 23462 \| HEY1 \| 1.692 \| DISEASES 26508 \| HEYL \| 1.205 \| DISEASES 5654 \| HTRA1 \| 5.549 \| DISEASES 3714 \| JAG2 \| 2.246 \| DISEASES 4052 \| LTBP1 \| 1.489 \| DISEASES 145873 \| MESP2 \| 3.201 \| DISEASES 4524 \| MTHFR \| 1.185 \| DISEASES 4553 \| MT-TA \| 2.074 \| DISEASES 4855 \| NOTCH4 \| 8.396 \| DISEASES 344022 \| NOTO \| 1.447 \| DISEASES 27445 \| PCLO \| 2.577 \| DISEASES 11235 \| PDCD10 \| 1.088 \| DISEASES 5144 \| PDE4D \| 2.732 \| DISEASES 51177 \| PLEKHO1 \| 2.079 \| DISEASES 23509 \| POFUT1 \| 2.684 \| DISEASES 5424 \| POLD1 \| 1.231 \| DISEASES 5454 \| POU3F2 \| 1.218 \| DISEASES 5663 \| PSEN1 \| 1.676 \| DISEASES 5664 \| PSEN2 \| 1.474 \| DISEASES 3516 \| RBPJ \| 3.545 \| DISEASES 54345 \| SOX18 \| 1.497 \| DISEASES 8831 \| SYNGAP1 \| 1.264 \| DISEASES 25816 \| TNFAIP8 \| 1.661 \| DISEASES 11277 \| TREX1 \| 4.37 \| DISEASES
Locus	Symbol \| Locus(Total Locus:1) NOTCH3 \| 19p13.12

Disease ID	436
Disease	cadasil
Integrated Phenotype	HPO \| Name(Total Integrated Phenotypes:37) HP:0100576 \| Amaurosis fugax HP:0000365 \| Hearing impairment HP:0002354 \| Memory impairment HP:0002637 \| Cerebral ischemia HP:0002376 \| Developmental regression HP:0006532 \| Recurrent pneumonia HP:0001257 \| Spasticity HP:0003236 \| Elevated serum creatine phosphokinase HP:0001289 \| Confusion HP:0009830 \| Peripheral neuropathy HP:0000822 \| Hypertension HP:0001943 \| Hypoglycemia HP:0002120 \| Cerebral cortical atrophy HP:0000407 \| Sensorineural hearing impairment HP:0001276 \| Hypertonia HP:0002353 \| EEG abnormality HP:0001250 \| Seizures HP:0002071 \| Abnormality of extrapyramidal motor function HP:0000763 \| Sensory neuropathy HP:0001288 \| Gait disturbance HP:0002301 \| Hemiplegia HP:0001259 \| Coma HP:0000726 \| Dementia HP:0001945 \| Fever HP:0002076 \| Migraine HP:0001933 \| Subcutaneous hemorrhage HP:0000505 \| Visual impairment HP:0100309 \| Subdural hemorrhage HP:0001136 \| Retinal arteriolar tortuosity HP:0000716 \| Depression HP:0006824 \| Cranial nerve paralysis HP:0007328 \| Impaired pain sensation HP:0002619 \| Varicose veins HP:0012639 \| Abnormality of nervous system morphology HP:0002381 \| Aphasia HP:0002315 \| Headache HP:0002621 \| Atherosclerosis
Text Mined Phenotype	HPO \| Name \| Sentences' Count(Total Phenotypes:17) HP:0001297 \| Cerebral vascular events \| 5 HP:0002315 \| Headaches \| 3 HP:0000726 \| Dementia \| 3 HP:0000822 \| Hypertension \| 3 HP:0002076 \| Migraine headaches \| 2 HP:0100543 \| Cognitive deficits \| 2 HP:0002511 \| Late-onset form of familial Alzheimer disease \| 1 HP:0002140 \| Ischemic stroke \| 1 HP:0001513 \| Obesity \| 1 HP:0007302 \| Bipolar disorder \| 1 HP:0002015 \| Swallowing difficulty \| 1 HP:0000708 \| Behavioral problems \| 1 HP:0002960 \| Autoimmune condition \| 1 HP:0002133 \| Status epilepticus \| 1 HP:0003077 \| Hyperlipidemia \| 1 HP:0001677 \| Coronary artery disease \| 1 HP:0001342 \| Intracerebral hemorrhage \| 1

Disease ID	436
Disease	cadasil
Manually Symptom	(Waiting for update.)
Text Mined Symptom	(Waiting for update.)

Manually Genotype(Total Text Mining Genotypes:0)
(Waiting for update.)

Text Mining Genotype(Total Genotypes:0)
(Waiting for update.)

All Snps(Total Genotypes:18)
snpId	pubmedId	geneId	geneSymbol	diseaseId	sourceId	sentence	score	Year	geneSymbol_dbSNP	CHROMOSOME	POS	REF	ALT
rs137852641	15694192	4854	NOTCH3	umls:C0751587	BeFree	Arg332Cys mutation of NOTCH3 gene in the first known Taiwanese family with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy.	0.537478391	2005	NOTCH3	19	15191466	G	A
rs137852642	16807713	4854	NOTCH3	umls:C0751587	BeFree	We have previously described a patient with CADASIL caused by a R133C mutation in the NOTCH3 gene and with a concomitant myopathy caused by a 5650G>A mutation in the MTTA gene in mitochondrial DNA (mtDNA).	0.537478391	2006	NOTCH3	19	15192242	G	T,A
rs137852642	15851739	4854	NOTCH3	umls:C0751587	BeFree	Based on a structured questionnaire and medical records, the authors found that 12 of 25 mothers with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) with the R133C NOTCH3 mutation had had neurologic symptoms in 17 of their 43 pregnancies, most commonly hemiparesthesia (76%), hemiparesis (36%), aphasia (65%), and visual disorders (47%).	0.537478391	2005	NOTCH3	19	15192242	G	T,A
rs137852642	15143298	4854	NOTCH3	umls:C0751587	BeFree	The aim of this study was to characterize cognitive function in subjects with a C475T (R133C) mutation in the Notch3 gene, leading to CADASIL.	0.537478391	2004	NOTCH3	19	15192242	G	T,A
rs137852642	10969905	4854	NOTCH3	umls:C0751587	BeFree	Arg133Cys mutation of Notch3 in two unrelated Japanese families with CADASIL.	0.537478391	2000	NOTCH3	19	15192242	G	T,A
rs137852642	17276737	4854	NOTCH3	umls:C0751587	BeFree	We have previously described a patient with cerebral autosomal-dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) caused by R133C mutation in NOTCH3 and with a concomitant myopathy caused by a G to A point mutation at base pair 5650 (5650G>A) in the gene encoding tRNA(Ala) in mitochondrial DNA (mtDNA).	0.537478391	2007	NOTCH3	19	15192242	G	T,A
rs137852642	15605982	4854	NOTCH3	umls:C0751587	BeFree	To verify whether true stenosis of the fibrotic white matter arteries is a key pathogenic event in CADASIL, we analyzed the thickness of walls (expressed as sclerotic index) and luminal diameters of penetrating arterioles in both grey matter and white matter of four CADASIL patients due to the C475T (R133C) mutation in the Notch3 gene and in 9 age-matched controls.	0.537478391	2004	NOTCH3	19	15192242	G	T,A
rs137852642	11486103	4854	NOTCH3	umls:C0751587	BeFree	Phenotype of a homozygous CADASIL patient in comparison to 9 age-matched heterozygous patients with the same R133C Notch3 mutation.	0.537478391	2001	NOTCH3	19	15192242	G	T,A
rs201118034	10371548	4854	NOTCH3	umls:C0751587	UNIPROT	Diagnostic Notch3 sequence analysis in CADASIL: three new mutations in Dutch patients. Dutch CADASIL Research Group.	0.537478391	1999	NOTCH3	19	15187315	G	A
rs201118034	21852154	4854	NOTCH3	umls:C0751587	BeFree	Diversity of stroke presentation in CADASIL: study from patients harboring the predominant NOTCH3 mutation R544C.	0.537478391	2013	NOTCH3	19	15187315	G	A
rs201118034	25692567	4854	NOTCH3	umls:C0751587	BeFree	Clinical significance of cerebral microbleeds locations in CADASIL with R544C NOTCH3 mutation.	0.537478391	2015	NOTCH3	19	15187315	G	A
rs201680145	22153900	4854	NOTCH3	umls:C0751587	BeFree	We performed whole exome sequencing in a Turkish patient clinically diagnosed with Alzheimer's disease from a consanguineous family with a complex history of neurological and immunological disorders and identified a mutation in NOTCH3 (p.R1231C), previously described as causing cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL).	0.537478391	2012	NOTCH3;MIR6795	19	15179052	G	A
rs201680145	11102981	4854	NOTCH3	umls:C0751587	UNIPROT	We further performed Notch3 mutational scanning in five patients suspected of CADASIL diagnosis in which previous scanning, including SSCP and heteroduplexes analysis, failed to detect any pathogenic mutation.	0.537478391	2000	NOTCH3;MIR6795	19	15179052	G	A
rs28933696	10227618	4854	NOTCH3	umls:C0751587	UNIPROT	CADASIL is a hereditary form of small-vessel disease caused by mutations within the Notch3 gene.	0.537478391	1999	NOTCH3	19	15192134	G	A
rs28933697	10227618	4854	NOTCH3	umls:C0751587	UNIPROT	CADASIL is a hereditary form of small-vessel disease caused by mutations within the Notch3 gene.	0.537478391	1999	NOTCH3	19	15192095	G	A
rs28933698	12136071	4854	NOTCH3	umls:C0751587	BeFree	C455R notch3 mutation in a Colombian CADASIL kindred with early onset of stroke.	0.537478391	2002	NOTCH3	19	15189004	A	G
rs28933698	12136071	4854	NOTCH3	umls:C0751587	UNIPROT	C455R notch3 mutation in a Colombian CADASIL kindred with early onset of stroke.	0.537478391	2002	NOTCH3	19	15189004	A	G
rs28937321	9388399	4854	NOTCH3	umls:C0751587	UNIPROT	Strong clustering and stereotyped nature of Notch3 mutations in CADASIL patients.	0.537478391	1997	NOTCH3	19	15192504	C	A

GWASdb Annotation(Total Genotypes:0)
(Waiting for update.)

GWASdb Snp Trait(Total Genotypes:0)
(Waiting for update.)

Mapped by lexical matching(Total Items:9)
HP ID	HP Name	MP ID	MP Name	Annotation
HP:0001933	Subcutaneous hemorrhage	MP:0011437	glomerulus hemorrhage	bleeding in the renal glomerulus
HP:0002637	Cerebral ischemia	MP:0006190	retinal ischemia	inadequate blood flow to the retina usually due to functional constriction or obstruction of a blood vessel
HP:0000407	Sensorineural hearing impairment	MP:0006330	syndromic hearing impairment	hearing impairment that is usually associated with malformations of the external ear and other inherited signs and symptoms
HP:0002120	Cerebral cortical atrophy	MP:0012506	brain atrophy	acquired diminution of the size of the brain associated with wasting as from death and reabsorbtion of cells, diminished cellular proliferation, decreased cellular volume, pressure, ischemia, malnutrition, reduced function or malfunction, or hormonal chan
HP:0003236	Elevated serum creatine phosphokinase	MP:0020280	increased creatine kinase level	increased level of the enzyme that catalyzes the reversible transfer of creatine to phosphocreatine
HP:0007328	Impaired pain sensation	MP:0001970	abnormal pain threshold	increased or decreased average level of perception of pain
HP:0006824	Cranial nerve paralysis	MP:0006303	abnormal retinal nerve fiber layer morphology	any structural anomaly of the layer of the retina formed by expansion of the fibers of the optic nerve
HP:0006532	Recurrent pneumonia	MP:0001862	interstitial pneumonia	any of a group of inflammatory and fibrotic disorders of the lower respiratory tract, primarily affecting the supporting framework of the lung, including the alveolar wall, but may also involve the small airways and blood vessels of the lung parenchyma
HP:0002071	Abnormality of extrapyramidal motor function	MP:0009403	increased variability of skeletal muscle fiber size	greater range or dispersion within a distribution of skeletal muscle fiber size within a muscle compared to controls

Mapped by homologous gene(Total Items:35)
HP ID	HP Name	MP ID	MP Name	Annotation
HP:0001945	Fever	MP:0020254	decreased collagen level	decreased level of the main structural protein of the various connective tissues in animals
HP:0002381	Aphasia	MP:0020329	decreased capillary density	reduction in the number of capillaries in a given cross-sectional area of a tissue
HP:0002120	Cerebral cortical atrophy	MP:0020329	decreased capillary density	reduction in the number of capillaries in a given cross-sectional area of a tissue
HP:0002315	Headache	MP:0020137	decreased bone mineralization	decrease in the rate at which minerals are deposited into bone
HP:0001250	Seizures	MP:3000003	abnormal Ebner's gland morphology	any structural anomaly of the serous salivary glands which reside adjacent to the moats surrounding the circumvallate and foliate papillae just anterior to the posterior third of the tongue, anterior to the terminal sulcus; these exocrine glands secrete l
HP:0001259	Coma	MP:0020216	decreased circulating complement protein level	less than normal levels of the serum proteins that act sequentially to allow for the direct killing of microbes, the disposal of immune complexes, and the regulation of other immune processes
HP:0002353	EEG abnormality	MP:0020214	susceptible to malignant hyperthermia	increased susceptibility to hyperthermia triggered by exposure to certain drugs used for general anesthesia, specifically the volatile anesthetic agents and the neuromuscular blocking agent, succinylcholine
HP:0009830	Peripheral neuropathy	MP:0020137	decreased bone mineralization	decrease in the rate at which minerals are deposited into bone
HP:0001288	Gait disturbance	MP:0020329	decreased capillary density	reduction in the number of capillaries in a given cross-sectional area of a tissue
HP:0000407	Sensorineural hearing impairment	MP:3000003	abnormal Ebner's gland morphology	any structural anomaly of the serous salivary glands which reside adjacent to the moats surrounding the circumvallate and foliate papillae just anterior to the posterior third of the tongue, anterior to the terminal sulcus; these exocrine glands secrete l
HP:0002301	Hemiplegia	MP:0020215	impaired blood coagulation	impaired ability of the blood to clot
HP:0001257	Spasticity	MP:0020316	decreased vascular endothelial cell proliferation	decrease in the expansion rate of any vascular endothelial cell population by cell division
HP:0006824	Cranial nerve paralysis	MP:0020137	decreased bone mineralization	decrease in the rate at which minerals are deposited into bone
HP:0001136	Retinal arteriolar tortuosity	MP:0011697	vacuolated lens	fluid filled cavities are present in the cytoplasm of the transparent structure of the eye responsible for focusing light
HP:0002619	Varicose veins	MP:0011967	increased or absent threshold for auditory brainstem response	increase in the value at which one or more sound frequencies or broadband clicks first elicits a recordable response generated by electrical activity of neurons in the ascending auditory system, or complete lack of a recordable response at any frequency o
HP:0100576	Amaurosis fugax	MP:0014071	increased cardiac muscle glycogen level	greater than the normal concentration of a readily converted carbohydrate reserve in heart muscle
HP:0002637	Cerebral ischemia	MP:0014206	decreased intestinal epithelial sodium ion transmembrane transport
HP:0006532	Recurrent pneumonia	MP:0020254	decreased collagen level	decreased level of the main structural protein of the various connective tissues in animals
HP:0003236	Elevated serum creatine phosphokinase	MP:0020309	increased creatine kinase activity	increased ability of to catalyze the reaction: ATP + creatine = N-phosphocreatine + ADP + 2 H(+).
HP:0001943	Hypoglycemia	MP:0020137	decreased bone mineralization	decrease in the rate at which minerals are deposited into bone
HP:0002621	Atherosclerosis	MP:0020137	decreased bone mineralization	decrease in the rate at which minerals are deposited into bone
HP:0001276	Hypertonia	MP:0020316	decreased vascular endothelial cell proliferation	decrease in the expansion rate of any vascular endothelial cell population by cell division
HP:0002376	Developmental regression	MP:0020214	susceptible to malignant hyperthermia	increased susceptibility to hyperthermia triggered by exposure to certain drugs used for general anesthesia, specifically the volatile anesthetic agents and the neuromuscular blocking agent, succinylcholine
HP:0000365	Hearing impairment	MP:0020254	decreased collagen level	decreased level of the main structural protein of the various connective tissues in animals
HP:0002071	Abnormality of extrapyramidal motor function	MP:0020329	decreased capillary density	reduction in the number of capillaries in a given cross-sectional area of a tissue
HP:0002076	Migraine	MP:0020329	decreased capillary density	reduction in the number of capillaries in a given cross-sectional area of a tissue
HP:0000726	Dementia	MP:0020329	decreased capillary density	reduction in the number of capillaries in a given cross-sectional area of a tissue
HP:0002354	Memory impairment	MP:0020329	decreased capillary density	reduction in the number of capillaries in a given cross-sectional area of a tissue
HP:0001289	Confusion	MP:0020187	altered susceptibility to prion infection	altered likelihood that an organism will develop ill effects from the small proteinaceous infectious particles which are resistant to inactivation by procedures that modify nucleic acids and which contain an abnormal isoform of a cellular protein that is
HP:0001933	Subcutaneous hemorrhage	MP:0020329	decreased capillary density	reduction in the number of capillaries in a given cross-sectional area of a tissue
HP:0000716	Depression	MP:0020329	decreased capillary density	reduction in the number of capillaries in a given cross-sectional area of a tissue
HP:0007328	Impaired pain sensation	MP:0014124	increased amylin secretion	greater than normal production or release of the polypeptide hormone that is normally co-secreted with insulin by the beta cells of the pancreatic islets of Langerhans and is known to inhibit glucagon secretion, delay gastric emptying, and act as a satiet
HP:0000505	Visual impairment	MP:3000003	abnormal Ebner's gland morphology	any structural anomaly of the serous salivary glands which reside adjacent to the moats surrounding the circumvallate and foliate papillae just anterior to the posterior third of the tongue, anterior to the terminal sulcus; these exocrine glands secrete l
HP:0000822	Hypertension	MP:0020216	decreased circulating complement protein level	less than normal levels of the serum proteins that act sequentially to allow for the direct killing of microbes, the disposal of immune complexes, and the regulation of other immune processes
HP:0000763	Sensory neuropathy	MP:0014185	cerebellum atrophy	acquired diminution of the size of the cerebellum associated with wasting as from death and reabsorption of cells, diminished cellular proliferation, decreased cellular volume, pressure, ischemia, malnutrition, reduced function or malfunction, or hormonal

Disease ID	436
Disease	cadasil
Case	(Waiting for update.)