H01619 | |
H number | H01619 |
Name | Primary pulmonary hypertension |
Description | Primary pulmonary hypertension (PPH) is a progressive disease characterised by raised pulmonary vascular resistance, which results in diminished right-heart function due to increased right ventricular afterload. PPH occurs most commonly in young and middle-aged women; mean survival from onset of symptoms is 2-3 years. Mutations in the type II bone morphogenetic protein (BMP) receptor (BMPR)-II are now considered to be the genetic basis for familial PPH and ~30% of cases of sporadic PPH. BMPs are members of the transforming growth factor beta superfamily and affect intracellular signalling via Smads and mitogen-activated protein kinases. It has been shown that missense mutations of cysteine residues in the extracellular or kinase domain of BMPR2 result in intracellular localisation of the mutated receptor and negligible Smad signalling. |
Category | Cardiovascular disease |
Network | nt06507(H01619) TGFB signaling |
Gene | (PPH1) BMPR2 [HSA:659] [KO:K04671] (PPH2) SMAD9 [HSA:4093] [KO:K16791] (PPH3) CAV1 [HSA:857] [KO:K06278] (PPH4) KCNK3 [HSA:3777] [KO:K04914] |
Pathogen | - |
Env factor | - |
Carcinogen | - |
Drug | Nitric oxide [DR:D00074] |
Comment | - |
Other DBs | ICD-11: BB01 ICD-10: I27.0 MeSH: D065627 OMIM: 178600 615342 615343 615344 |
Reference | PMID:9729004 AUTHORS Gaine SP, Rubin LJ TITLE Primary pulmonary hypertension. JOURNAL Lancet 352:719-25 (1998) DOI:10.1016/S0140-6736(98)02111-4 PMID:12737878 (PPH1) AUTHORS Runo JR, Loyd JE TITLE Primary pulmonary hypertension. JOURNAL Lancet 361:1533-44 (2003) DOI:10.1016/S0140-6736(03)13167-4 PMID:15005857 AUTHORS Rudarakanchana N, Morrell NW TITLE Primary pulmonary hypertension: molecular basis and potential for therapy. JOURNAL Expert Rev Mol Med 6:1-15 (2004) DOI:10.1017/S1462399404007483 PMID:12503718 AUTHORS Eddahibi S, Morrell N, d'Ortho MP, Naeije R, Adnot S TITLE Pathobiology of pulmonary arterial hypertension. JOURNAL Eur Respir J 20:1559-72 (2002) DOI:10.1183/09031936.02.00081302 PMID:19211612 (PPH2) AUTHORS Shintani M, Yagi H, Nakayama T, Saji T, Matsuoka R TITLE A new nonsense mutation of SMAD8 associated with pulmonary arterial hypertension. JOURNAL J Med Genet 46:331-7 (2009) DOI:10.1136/jmg.2008.062703 PMID:22474227 (PPH3) AUTHORS Austin ED, Ma L, LeDuc C, Berman Rosenzweig E, Borczuk A, Phillips JA 3rd, Palomero T, Sumazin P, Kim HR, Talati MH, West J, Loyd JE, Chung WK TITLE Whole exome sequencing to identify a novel gene (caveolin-1) associated with human pulmonary arterial hypertension. JOURNAL Circ Cardiovasc Genet 5:336-43 (2012) DOI:10.1161/CIRCGENETICS.111.961888 PMID:23883380 (PPH4) AUTHORS Ma L, Roman-Campos D, Austin ED, Eyries M, Sampson KS, Soubrier F, Germain M, Tregouet DA, Borczuk A, Rosenzweig EB, Girerd B, Montani D, Humbert M, Loyd JE, Kass RS, Chung WK TITLE A novel channelopathy in pulmonary arterial hypertension. JOURNAL N Engl J Med 369:351-361 (2013) DOI:10.1056/NEJMoa1211097 |