eRAM
encyclopedia of Rare Disease Annotation for Precision Medicine
| pulmonary arterial hypertension | ||||
| Disease ID | 489 |
|---|---|
| Disease | pulmonary arterial hypertension |
| Definition | Pulmonary arterial hypertension (PAH) is a rare, progressive disorder characterized by high blood pressure (hypertension) in the arteries of the lungs (pulmonary artery) for no apparent reason. The pulmonary arteries are the blood vessels that carry blood from the right side of the heart through the lungs. Symptoms of PAH include shortness of breath (dyspnea) especially during exercise, chest pain, and fainting episodes. The exact cause of PAH is unknown and although treatable, there is no known cure for the disease. PAH usually affects women between the ages of 30-60. Individuals with PAH may go years without a diagnosis, either because their symptoms are mild, nonspecific, or only present during demanding exercise. However, it is important to treat PAH because without treatment high blood pressure in the lungs causes the right heart to work much harder, and over time, this heart muscle may weaken or fail. The progressive nature of this disease means that an individual may experience only mild symptoms at first, but will eventually require treatment and medical care to maintain a normal lifestyle.Approximately 15-20% of patients with PAH have heritable PAH. People with heritable PAH have either: (1) an autosomal dominant genetic condition associated with mutations in the BMPR2 gene or another gene in the TGFbeta pathway or other recently identified pathway now associated with HPAH, or (2) are members of a family in which PAH is known to occur as primary disease.The first reported case of PAH occurred in 1891, when the German?doctor 燛. Romberg published a description of a patient who, at autopsy, showed thickening of the pulmonary artery but no heart or lung disease that might have caused the condition. In 1951, 3 cases were reported by Dr. D.T. Dresdale in the U.S. and the illness was originally called primary pulmonary hypertension. PAH has been linked to diet drugs such as Fen-Phen, Pondimin and Redux. These drugs were taken off the market in 1997, although cases related to drugs and toxins, such as methamphetamines do still appear. PAH is also associated with a number of other medical diseases such as cirrhosis and connective tissue diseases like scleroderma. About 30% of patients with PAH have an associated connective tissue disease. - NORD Reference: NORD |
| Synonym | hypertensive pulmonary arterial disease pulmonary hypertensive arterial disease pulmonary hypertensive arterial disease (disorder) |
| Orphanet | |
| OMIM | |
| UMLS | C2973725 |
| SNOMED-CT | |
| Comorbidity | UMLS | Disease | Sentences' Count(Total Sentences:96) C0018799 | heart disease | 54 C0152021 | congenital heart disease | 52 C0036421 | systemic sclerosis | 39 C0009782 | connective tissue disease | 32 C0009782 | connective tissue diseases | 18 C0018801 | heart failure | 14 C0020541 | portal hypertension | 12 C0020542 | pulmonary hypertension | 7 C0020538 | hypertension | 6 C0011644 | scleroderma | 5 C0031039 | pericardial effusion | 5 C0024141 | systemic lupus erythematosus | 5 C0018799 | heart diseases | 4 C0153500 | heart ca | 4 C0039445 | hereditary hemorrhagic telangiectasia | 4 C0039730 | thalassemia | 4 C0024115 | lung disease | 4 C0042373 | vascular disease | 3 C0085253 | adult-onset still's disease | 2 C0036323 | schistosomiasis | 2 C1145670 | respiratory failure | 2 C0011570 | depression | 2 C0031039 | pericardial effusions | 2 C0016522 | secundum atrial septal defect | 2 C0085113 | neurofibromatosis | 2 C0034091 | pulmonary veno-occlusive disease | 2 C0002895 | sickle cell disease | 2 C0026272 | mixed connective tissue disease | 2 C0039446 | telangiectasia | 2 C0018818 | ventricular septal defect | 2 C0006287 | bronchopulmonary dysplasia | 2 C0026654 | moyamoya | 2 C0005283 | beta thalassemia | 1 C0019158 | hepatitis | 1 C0748540 | limited systemic sclerosis | 1 C0035435 | rheumatic diseases | 1 C0020550 | hyperthyroidism | 1 C0029454 | osteopetrosis | 1 C0024117 | chronic obstructive lung disease | 1 C0024117 | chronic obstructive pulmonary disease | 1 C0024117 | chronic obstructive pulmonary disease (copd) | 1 C0022658 | renal disease | 1 C1561644 | chronic kidney disease (ckd) | 1 C0010068 | coronary artery disease | 1 C0206138 | crest syndrome | 1 C0023448 | lymphoblastic leukemia | 1 C0018553 | cowden syndrome | 1 C0040961 | tricuspid regurgitation | 1 C0022661 | chronic kidney disease | 1 C1527336 | sjogren's syndrome | 1 C0034063 | pulmonary edema | 1 C0026986 | myelodysplastic syndrome | 1 C0024299 | lymphoma | 1 C0852949 | arteriopathy | 1 C0175703 | tar syndrome | 1 C0026654 | moyamoya disease | 1 C0035222 | acute respiratory distress syndrome | 1 C0024115 | lung disorders | 1 C0003507 | aortic stenosis | 1 C1700942 | idiopathic pulmonary arterial hypertension | 1 C0028754 | obesity | 1 C0206062 | interstitial lung disease | 1 C0024115 | pulmonary disease | 1 C0013384 | dyskinesia | 1 C0241910 | autoimmune hepatitis | 1 C0042974 | von willebrand disease | 1 C0022661 | end-stage renal disease | 1 C0409974 | lupus erythematosus | 1 C1290344 | nonspecific interstitial pneumonia | 1 C0034069 | pulmonary fibrosis | 1 C1800706 | idiopathic pulmonary fibrosis | 1 C0024314 | lymphoproliferative disorder | 1 C0338484 | familial hemiplegic migraine | 1 C0023418 | leukemia | 1 C0038012 | spondylitis | 1 C0037315 | sleep apnea | 1 C0026265 | mitral valve disease | 1 C0018802 | congestive heart failure | 1 C0023449 | acute lymphoblastic leukemia | 1 C0030499 | parasitic disease | 1 C0018816 | septal defects | 1 C0024314 | lymphoproliferative disorders | 1 C0040128 | thyroid disease | 1 C0023895 | liver disease | 1 C0018818 | ventricular septal defects | 1 C0740394 | hyperuricemia | 1 C0038013 | ankylosing spondylitis | 1 C0600260 | obstructive pulmonary disease | 1 C0035435 | rheumatic disease | 1 C0018213 | graves' disease | 1 C0008780 | primary ciliary dyskinesia | 1 C0002871 | anemia | 1 C0026654 | moyamoya syndrome | 1 C0032285 | pneumonia | 1 C0398623 | hypercoagulability | 1 C0022658 | kidney disease | 1 |
| Curated Gene | (Waiting for update.) |
| Inferring Gene | (Waiting for update.) |
| Text Mined Gene | (Waiting for update.) |
| Locus | (Waiting for update.) |
| Disease ID | 489 |
|---|---|
| Disease | pulmonary arterial hypertension |
| Manually Symptom | UMLS | Name(Total Manually Symptoms:23) C2707258 | infections C2364133 | infection C2024883 | angina C1402315 | vascular lesions C0856169 | endothelial dysfunction C0742006 | catheter infection C0264714 | acute heart failure C0241910 | autoimmune hepatitis C0238074 | chronic cor pulmonale C0235527 | right ventricular failure C0235527 | right heart failure C0178468 | autoimmune thyroid disease C0087086 | thrombi C0040034 | thrombocytopenia C0031039 | pericardial effusions C0030499 | parasitic disease C0026272 | mixed connective tissue disease C0024117 | chronic obstructive pulmonary disease (copd) C0023788 | whipple disease C0019079 | hemoptysis C0018816 | cardiac septal defects C0004096 | asthma C0002940 | aneurysm |
| Text Mined Symptom | UMLS | Name | Sentences' Count(Total Symptoms:14) C0235527 | right heart failure | 8 C0856169 | endothelial dysfunction | 6 C0235527 | right ventricular failure | 5 C0002940 | aneurysm | 3 C0031039 | pericardial effusions | 2 C1402315 | vascular lesions | 2 C0009450 | infection | 2 C0002962 | angina | 1 C0021311 | infections | 1 C0030499 | parasitic disease | 1 C0264714 | acute heart failure | 1 C0241910 | autoimmune hepatitis | 1 C0026272 | mixed connective tissue disease | 1 C0024117 | chronic obstructive pulmonary disease (copd) | 1 |
Manually Genotype(Total Manually Genotypes:12) | |||
|---|---|---|---|
| Gene | Mutation | DOI | Article Title |
| - | c.16C>T； p.Glu5X | 10.1038/gim.2013.41 | Alu-mediated nonallelic homologous and nonhomologous recombination in the BMPR2 gene in heritable pulmonary arterial hypertension |
| - | c.201insA ；p.Tyr67X | 10.1038/gim.2013.41 | Alu-mediated nonallelic homologous and nonhomologous recombination in the BMPR3 gene in heritable pulmonary arterial hypertension |
| - | c.237delT ；p.Leu79fsX2 | 10.1038/gim.2013.41 | Alu-mediated nonallelic homologous and nonhomologous recombination in the BMPR4 gene in heritable pulmonary arterial hypertension |
| - | c.255G>A ；p.Trp85X | 10.1038/gim.2013.41 | Alu-mediated nonallelic homologous and nonhomologous recombination in the BMPR5 gene in heritable pulmonary arterial hypertension |
| - | c.399insA； p.Tyr113X | 10.1038/gim.2013.41 | Alu-mediated nonallelic homologous and nonhomologous recombination in the BMPR6 gene in heritable pulmonary arterial hypertension |
| - | c.498delT ；p.Val166fsX9 | 10.1038/gim.2013.41 | Alu-mediated nonallelic homologous and nonhomologous recombination in the BMPR7 gene in heritable pulmonary arterial hypertension |
| - | c.853-2A>G | 10.1038/gim.2013.41 | Alu-mediated nonallelic homologous and nonhomologous recombination in the BMPR8 gene in heritable pulmonary arterial hypertension |
| - | c.1016T>A； p.Val339Asp | 10.1038/gim.2013.41 | Alu-mediated nonallelic homologous and nonhomologous recombination in the BMPR9 gene in heritable pulmonary arterial hypertension |
| - | c.1969insA； p.Gln657fsX17 | 10.1038/gim.2013.41 | Alu-mediated nonallelic homologous and nonhomologous recombination in the BMPR10 gene in heritable pulmonary arterial hypertension |
| - | c.2128delC ；p.Leu710fsX2 | 10.1038/gim.2013.41 | Alu-mediated nonallelic homologous and nonhomologous recombination in the BMPR11 gene in heritable pulmonary arterial hypertension |
| - | c.1-128k_418+7kdel | 10.1038/gim.2013.41 | Alu-mediated nonallelic homologous and nonhomologous recombination in the BMPR12 gene in heritable pulmonary arterial hypertension |
| - | c.1277-291_1413+4735del | 10.1038/gim.2013.41 | Alu-mediated nonallelic homologous and nonhomologous recombination in the BMPR13 gene in heritable pulmonary arterial hypertension |
Text Mining Genotype(Total Genotypes:0) | |
|---|---|
| (Waiting for update.) | |
All Snps(Total Genotypes:5) | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| snpId | pubmedId | geneId | geneSymbol | diseaseId | sourceId | sentence | score | Year | geneSymbol_dbSNP | CHROMOSOME | POS | REF | ALT |
| rs10744676 | 20556823 | 3741 | KCNA5 | umls:C2973725 | BeFree | Our results provide the first evidence for an association between the KCNA5 rs10744676 variant and PAH associated with SSc. | 0.001628651 | 2010 | KCNA5 | 12 | 5043783 | C | T |
| rs137852741 | 21622843 | 659 | BMPR2 | umls:C2973725 | BeFree | Three BMPR2 mutants, D485G, N519K, and R899X, which are known to be involved in PAH, were chosen as our model system. | 0.025515536 | 2011 | BMPR2 | 2 | 202556360 | C | G,T |
| rs137852745 | 21622843 | 659 | BMPR2 | umls:C2973725 | BeFree | Three BMPR2 mutants, D485G, N519K, and R899X, which are known to be involved in PAH, were chosen as our model system. | 0.025515536 | 2011 | BMPR2 | 2 | 202552756 | A | G |
| rs344781 | 20967855 | 343170 | OR14K1 | umls:C2973725 | BeFree | In the Italian cohort, the rs344781 G allele was associated with SSc-related digital ulceration (odds ratio [OR] 1.39), pulmonary arterial hypertension (PAH) (OR 1.81), anticentromere antibody (ACA) positivity (OR 1.45), and limited cutaneous SSc (lcSSc) (OR 1.37). | 0.000271442 | 2011 | PLAUR | 19 | 43670636 | C | T |
| rs5743704 | 21905008 | 7097 | TLR2 | umls:C2973725 | BeFree | Among patients with SSc, the rare TLR2 Pro631His variant is robustly associated with antitopoisomerase positivity, the diffuse form of the disease, and the development of PAH. | 0.000271442 | 2012 | TLR2 | 4 | 153704799 | 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:5) | ||||
|---|---|---|---|---|
| HP ID | HP Name | MP ID | MP Name | Annotation |
| HP:0010741 | Edema of the lower limbs | MP:0009657 | failure of chorioallantoic fusion | failure to initiate and/or complete the formation of a highly vascularized extra-embryonic fetal membrane by fusion of the chorion and allantois |
| HP:0001702 | Abnormality of the tricuspid valve | MP:0010919 | increased number of pulmonary neuroendocrine bodies | greater number of the corpuscular, organoid structures composed of PNECs, found as distinctive innervated clusters only within intrapulmonary airways, where they appear concentrated at airway branch points; NEBs reach from the basement membrane to the air |
| HP:0001645 | Sudden cardiac death | MP:0012557 | decreased calcium uptake by cardiac muscle | decreased directed movement of calcium ions into cardiac muscle; decreased or disrupted uptake may give rise to energetic deficit and oxidative stress. leading to cardiac disease |
| HP:0002205 | Recurrent respiratory infections | MP:0014182 | decreased respiratory epithelial sodium ion transmembrane transport | decrease in the directed movement of sodium ions from one side of the respiratory epithelial cell membrane to the other |
| HP:0001635 | Congestive heart failure | MP:0011925 | abnormal heart echocardiography feature | any anomaly in echocardiographic representation of systolic and diastolic function, ventricular compliance, valvular function, or interventricular septum features |
Mapped by homologous gene(Total Items:15) | ||||
|---|---|---|---|---|
| HP ID | HP Name | MP ID | MP Name | Annotation |
| HP:0005306 | Capillary hemangiomas | MP:0013956 | decreased colon length | reduced length of the portion of the large intestine between the cecum and the rectum |
| HP:0001635 | Congestive heart failure | MP:0020329 | decreased capillary density | reduction in the number of capillaries in a given cross-sectional area of a tissue |
| HP:0002094 | Dyspnea | 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 |
| HP:0100749 | Chest pain | MP:0020154 | impaired humoral immune response | impaired response of the immune system that mediates secreted antibodies produced in B cells |
| HP:0002240 | Hepatomegaly | MP:0020329 | decreased capillary density | reduction in the number of capillaries in a given cross-sectional area of a tissue |
| HP:0001645 | Sudden cardiac death | MP:0020329 | decreased capillary density | reduction in the number of capillaries in a given cross-sectional area of a tissue |
| HP:0002205 | Recurrent respiratory infections | MP:0020321 | increased vascular endothelial cell apoptosis | increase in the timing or the number of vascular endothelial cells undergoing programmed cell death |
| HP:0001063 | Acrocyanosis | MP:0020137 | decreased bone mineralization | decrease in the rate at which minerals are deposited into bone |
| HP:0001702 | Abnormality of the tricuspid valve | MP:0011108 | embryonic lethality during organogenesis, incomplete penetrance | the appearance of lower than Mendelian ratios of organisms of a given genotype due to death of some, but not all of the organisms between embryo turning and the completion of organogenesis (Mus: E9-9.5 to less than E14) |
| HP:0001541 | Ascites | MP:0020137 | decreased bone mineralization | decrease in the rate at which minerals are deposited into bone |
| HP:0010741 | Edema of the lower limbs | MP:0013258 | abnormal extracellular matrix morphology | any structural anomaly of the structure lying external to one or more cells, which provides structural support for cells or tissues; in mammals, the extracellular matrix is completely external to the cell |
| HP:0001962 | Palpitations | MP:0020329 | decreased capillary density | reduction in the number of capillaries in a given cross-sectional area of a tissue |
| HP:0012378 | Fatigue | MP:0013659 | abnormal erythroid lineage cell morphology | any structural anomaly of an immature or mature cell in the lineage leading to and including erythrocytes |
| HP:0002105 | Hemoptysis | MP:0011098 | embryonic lethality during organogenesis, complete penetrance | death of all organisms of a given genotype in a population between embryo turning and the completion of organogenesis (Mus: E9-9.5 to less than E14) |
| HP:0002321 | Vertigo | MP:0020329 | decreased capillary density | reduction in the number of capillaries in a given cross-sectional area of a tissue |
| Disease ID | 489 |
|---|---|
| Disease | pulmonary arterial hypertension |
| Case | (Waiting for update.) |