EIF2AK4 mutations cause pulmonary veno-occlusive disease, a recessive form of pulmonary hypertension

Nature Genetics

Volumn 46, Issue 1, 2014, Pages 65-69

  Eyries, Mélanie ^a,b,c   Montani, David ^d,e,f   Girerd, Barbara ^d,e,f   Perret, Claire ^c,g   Leroy, Anne ^b   Lonjou, Christine ^g   Chelghoum, Nadjim ^g   Coulet, Florence ^b,c   Bonnet, Damien ^g,h   Dorfmüller, Peter ^f   Fadel, Elie ^f   Sitbon, Olivier ^d,e,f   Simonneau, Gérald ^d,e,f   Tregouët, David Alexandre ^c,g   Humbert, Marc ^d,e,f   Soubrier, Florent ^a,b,c  

^a Institute OfCardiometabolism and Nutrition   (France)

^b ASSISTANCE PUBLIQUE HÔPITAUX DE PARIS   (France)

^c ICAN Institute for Cardiometabolism and Nutrition   (France)

^d UNIVERSITÉ PARIS SACLAY   (France)

^e BICÊTRE HOSPITAL   (France)

^f CENTRE CHIRURGICAL MARIE LANNELONGUE   (France)

^g INSERM   (France)

^h HÔPITAL NECKER ENFANTS MALADES   (France)

Author keywords

[No Author keywords available]

Indexed keywords

EIF2AK4 PROTEIN; INITIATION FACTOR 2ALPHA; UNCLASSIFIED DRUG;

ARTICLE; CAPILLARY PROLIFERATION; FRAMESHIFT MUTATION; GENE DISRUPTION; GENE FUNCTION; GENE MUTATION; GENE SEQUENCE; GENOTYPE; HETEROZYGOSITY; HISTOLOGY; HOMOZYGOSITY; HUMAN; IMMUNOHISTOCHEMISTRY; LUNG CAPILLARY; PENETRANCE; PRIORITY JOURNAL; PULMONARY HYPERTENSION; RECESSIVE GENE; WHOLE EXOME SEQUENCING;

EID: 84891373442     PISSN: 10614036     EISSN: 15461718     Source Type: Journal    
DOI: 10.1038/ng.2844     Document Type: Article

References (35)

1. Mandel, J., Mark, E.J. & Hales, C.A. Pulmonary veno-occlusive disease. Am. J. Respir. Crit. Care Med. 162, 1964-1973 (2000).
2. Montani, D. et al. Pulmonary veno-occlusive disease. Eur. Respir. J. 33, 189-200 (2009).
3. Simonneau, G. et al. Updated clinical classification of pulmonary hypertension. J. Am. Coll. Cardiol. 54, S43-S54 (2009).
4. Davies, P. & Reid, L. Pulmonary veno-occlusive disease in siblings: case reports and morphometric study. Hum. Pathol. 13, 911-915 (1982).
5. Heath, D., Segel, N. & Bishop, J. Pulmonary veno-occlusive disease. Circulation 34, 242-248 (1966).
6. Montani, D. et al. Pulmonary veno-occlusive disease: clinical, functional, radiologic, and hemodynamic characteristics and outcome of 24 cases confirmed by histology. Medicine 87, 220-233 (2008).
7. Trembath, R.C. et al. Clinical and molecular genetic features of pulmonary hypertension in patients with hereditary hemorrhagic telangiectasia. N. Engl. J. Med. 345, 325-334 (2001).
8. Girerd, B. et al. Clinical outcomes of pulmonary arterial hypertension in patients carrying an ACVRL1 (ALK1) mutation. Am. J. Respir. Crit. Care Med. 181, 851-861 (2010).
9. Machado, R.D. et al. Genetics and genomics of pulmonary arterial hypertension. J. Am. Coll. Cardiol. 54, S32-S42 (2009).
10. Rosenthal, A., Vawter, G. & Wagenvoort, C.A. Intrapulmonary veno-occlusive disease. Am. J. Cardiol. 31, 78-83 (1973).
11. Voordes, C.G., Kuipers, J.R. & Elema, J.D. Familial pulmonary veno-occlusive disease: a case report. Thorax 32, 763-766 (1977).
12. Larkin, E.K. et al. Longitudinal analysis casts doubt on the presence of genetic anticipation in heritable pulmonary arterial hypertension. Am. J. Respir. Crit. Care Med. 186, 892-896 (2012).
13. Humbert, M. et al. Pulmonary edema complicating continuous intravenous prostacyclin in pulmonary capillary hemangiomatosis. Am. J. Respir. Crit. Care Med. 157, 1681-1685 (1998).
14. Langleben, D. et al. Familial pulmonary capillary hemangiomatosis resulting in primary pulmonary hypertension. Ann. Intern. Med. 109, 106-109 (1988).
15. Lantuéjoul, S., Sheppard, M.N., Corrin, B., Burke, M.M. & Nicholson, A.G. Pulmonary veno-occlusive disease and pulmonary capillary hemangiomatosis: a clinicopathologic study of 35 cases. Am. J. Surg. Pathol. 30, 850-857 (2006).
16. Donnelly, N., Gorman, A.M., Gupta, S. & Samali, A. The eIF2? kinases: their structures and functions. Cell. Mol. Life Sci. 70, 3493-3511 (2013).
17. Anthony, T.G. et al. Preservation of liver protein synthesis during dietary leucine deprivation occurs at the expense of skeletal muscle mass in mice deleted for eIF2 kinase GCN2. J. Biol. Chem. 279, 36553-36561 (2004).
18. Chaveroux, C. et al. Identification of GCN2 as new redox regulator for oxidative stress prevention in vivo. Biochem. Biophys. Res. Commun. 415, 120-124 (2011).
19. Fessel, J.P. et al. Hyperoxia synergizes with mutant BMPR2 to cause metabolic stress, oxidant injury, and pulmonary hypertension. Am. J. Respir. Cell Mol. Biol. 49, 778-787 (2013).
20. Machado, R.D. et al. BMPR2 haploinsufficiency as the inherited molecular mechanism for primary pulmonary hypertension. Am. J. Hum. Genet. 68, 92-102 (2001).
21. Barrios-Rodiles, M. et al. High-throughput mapping of a dynamic signaling network in mammalian cells. Science 307, 1621-1625 (2005).
22. Carraro, V. et al. Amino acid availability controls TRB3 transcription in liver through the GCN2/eIF2?/ATF4 pathway. PLoS ONE 5, e15716 (2010).
23. Chan, M.C. et al. A novel regulatory mechanism of the bone morphogenetic protein (BMP) signaling pathway involving the carboxyl-terminal tail domain of BMP type II receptor. Mol. Cell. Biol. 27, 5776-5789 (2007).
24. Davies, R.J. et al. BMP type II receptor deficiency confers resistance to growth inhibition by TGF-? in pulmonary artery smooth muscle cells: role of proinflammatory cytokines. Am. J. Physiol. Lung Cell. Mol. Physiol. 302, L604-L615 (2012).
25. Sattlegger, E. & Hinnebusch, A.G. Separate domains in GCN1 for binding protein kinase GCN2 and ribosomes are required for GCN2 activation in amino acid-starved cells. EMBO J. 19, 6622-6633 (2000).
26. Humbert, M. et al. Pulmonary arterial hypertension in France: results from a national registry. Am. J. Respir. Crit. Care Med. 173, 1023-1030 (2006).
27. Sitbon, O. et al. Long-term response to calcium channel blockers in idiopathic pulmonary arterial hypertension. Circulation 111, 3105-3111 (2005).
28. Sztrymf, B. et al. Clinical outcomes of pulmonary arterial hypertension in carriers of BMPR2 mutation. Am. J. Respir. Crit. Care Med. 177, 1377-1383 (2008).
29. Eyries, M. et al. ACVRL1 germinal mosaic with two mutant alleles in hereditary hemorrhagic telangiectasia associated with pulmonary arterial hypertension. Clin. Genet. 82, 173-179 (2012).
30. O'Connell, J.R. & Weeks, D.E. PedCheck: a program for identification of genotype incompatibilities in linkage analysis. Am. J. Hum. Genet. 63, 259-266 (1998).
31. Abecasis, G.R., Cherny, S.S., Cookson, W.O. & Cardon, L.R. Merlin-rapid analysis of dense genetic maps using sparse gene flow trees. Nat. Genet. 30, 97-101 (2002).
32. Kong, A. & Cox, N.J. Allele-sharing models: LOD scores and accurate linkage tests. Am. J. Hum. Genet. 61, 1179-1188 (1997).
33. Barrett, J.C., Fry, B., Maller, J. & Daly, M.J. Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 21, 263-265 (2005).
34. Li, H. et al. The Sequence Alignment/Map format and SAMtools. Bioinformatics 25, 2078-2079 (2009).
35. Wang, K., Li, M. & Hakonarson, H. ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data. Nucleic Acids Res. 38, e164 (2010).