Research progress of syndromic and non-syndromic mitral valve prolapse and its genetics_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

ZHENG Xijin ¹ , WANG Haoxu ² ,  HUANG Huanlei ^1,3

1. South China University of Technology School of Medicine, Guangzhou, 510006, P. R. China;
2. The First Affiliated Hospital of Wenzhou Medical University, Yueqing Third People's Hospital, Wenzhou, 325000, Zhejiang, P. R. China;
3. Department of Cardiovascular Surgery, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, P. R. China;

Corresponding author：

HUANG Huanlei, Email: hhuanlei@hotmail.com

Keywords：

Mitral valve prolapse; myxoid degeneration; gene; review

DOI：

10.7507/1007-4848.202207013

Video：

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Abstract Full text Figures/Tables Video References Cited by

Mitral valve prolapse (MVP) is a common heart valve disease that affects 2%-3% of the general population. It can be manifested as mitral valve regurgitation and is the main indication for mitral valve surgery. MVP includes two forms of syndrome and non-syndrome. Syndromic MVP is associated with connective tissue diseases, such as Marfan syndrome. Non-syndromic MVP includes diffuse myxomatous mitral valve disease or Barlow’s disease and fibroelastic deficiency. MVP is a common disease in which late systolic clicks or mitral valve leaflets shift upward into the left atrium during ventricular systole, with or without mitral regurgitation. Echocardiography defines MVP as the prolapse of one or two leaflets of the mitral valve into the left atrium during systole, exceeding the level of the annulus line by more than 2 mm. In recent years, the development of genomics and imaging technology has enabled us to better understand the pathogenesis of MVP and provide possibilities for further prevention and treatment. This article reviews the research progress of MVP in epidemiology, etiology, histopathology, diagnosis and genetics.

Citation： ZHENG Xijin, WANG Haoxu, HUANG Huanlei. Research progress of syndromic and non-syndromic mitral valve prolapse and its genetics. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2023, 30(11): 1645-1650. doi: 10.7507/1007-4848.202207013 Copy

1.	Delling FN, Vasan RS. Epidemiology and pathophysiology of mitral valve prolapse: New insights into disease progression, genetics, and molecular basis. Circulation, 2014, 129(21): 2158-2170.
2.	Delling FN, Rong J, Larson MG, et al. Evolution of mitral valve prolapse: Insights from the Framingham heart study. Circulation, 2016, 133(17): 1688-1695.
3.	van Wijngaarden AL, Kruithof BPT, Vinella T, et al. Characterization of degenerative mitral valve disease: Differences between fibroelastic deficiency and Barlow's disease. J Cardiovasc Dev Dis, 2021, 8(2): 23.
4.	Hjortnaes J, Keegan J, Bruneval P, et al. Comparative histopathological analysis of mitral valves in Barlow disease and fibroelastic deficiency. Semin Thorac Cardiovasc Surg, 2016, 28(4): 757-767.
5.	Hei S, Iwataki M, Jang JY, et al. Relations of augmented systolic annular expansion and leaflet/papillary muscle dynamics in late-systolic mitral valve prolapse evaluated by echocardiography with a speckle tracking analysis. Int Heart J, 2020, 61(5): 970-978.
6.	Parwani P, Avierinos JF, Levine RA, et al. Mitral valve prolapse: Multimodality imaging and genetic insights. Prog Cardiovasc Dis, 2017, 60(3): 361-369.
7.	Freed LA, Levy D, Levine RA, et al. Prevalence and clinical outcome of mitral-valve prolapse. N Engl J Med, 1999, 341(1): 1-7.
8.	Perazzolo Marra M, Basso C. Mechanical dispersion and arrhythmic mitral valve prolapse: Aubstrate and trigger in electrical instability. Heart, 2019, 105(14): 1053-1054.
9.	Dziadzko V, Clavel MA, Dziadzko M, et al. Outcome and undertreatment of mitral regurgitation: A community cohort study. Lancet, 2018, 391(10124): 960-969.
10.	Meester JAN, Verstraeten A, Schepers D, et al. Differences in manifestations of Marfan syndrome, Ehlers-Danlos syndrome, and Loeys-Dietz syndrome. Ann Cardiothorac Surg, 2017, 6(6): 582-594.
11.	Spartalis M, Tzatzaki E, Spartalis E, et al. Mitral valve prolapse: An underestimated cause of sudden cardiac death—A current review of the literature. J Thorac Dis, 2017, 9(12): 5390-5398.
12.	Thacoor A. Mitral valve prolapse and Marfan syndrome. Congenit Heart Dis, 2017, 12(4): 430-434.
13.	Gasser S, Reichenspurner H, Girdauskas E. Genomic analysis in patients with myxomatous mitral valve prolapse: Current state of knowledge. BMC Cardiovasc Disord, 2018, 18(1): 41.
14.	Freed LA, Benjamin EJ, Levy D, et al. Mitral valve prolapse in the general population: The benign nature of echocardiographic features in the Framingham Heart Study. J Am Coll Cardiol, 2002, 40(7): 1298-1304.
15.	Disse S, Abergel E, Berrebi A, et al. Mapping of a first locus for autosomal dominant myxomatous mitral-valve prolapse to chromosome 16p11. 2-p12. 1. Am J Hum Genet, 1999, 65(5): 1242-1251.
16.	Freed LA, Acierno JS, Dai D, et al. A locus for autosomal dominant mitral valve prolapse on chromosome 11p15. 4. Am J Hum Genet, 2003, 72(6): 1551-1559.
17.	Nesta F, Leyne M, Yosefy C, et al. New locus for autosomal dominant mitral valve prolapse on chromosome 13: Clinical insights from genetic studies. Circulation, 2005, 112(13): 2022-2030.
18.	Le Tourneau T, Le Scouarnec S, Cueff C, et al. New insights into mitral valve dystrophy: A Filamin-A genotype-phenotype and outcome study. Eur Heart J, 2018, 39(15): 1269-1277.
19.	Kim KJ, Kim HK, Park JB, et al. Transthoracic echocardiographic findings of mitral regurgitation caused by commissural prolapse. JACC Cardiovasc Imaging, 2018, 11(6): 925-926.
20.	Militaru S, Bonnefous O, Hami K, et al. Validation of semiautomated quantification of mitral valve regurgitation by three-dimensional color Doppler transesophageal echocardiography. J Am Soc Echocardiogr, 2020, 33(3): 342-354.
21.	Berdejo J, Shiota M, Mihara H, et al. Vena contracta analysis by color Doppler three-dimensional transesophageal echocardiography shows geometrical differences between prolapse and pseudoprolapse in eccentric mitral regurgitation. Echocardiography, 2017, 34(5): 683-689.
22.	Gripari P, Mapelli M, Bellacosa I, et al. Transthoracic echocardiography in patients undergoing mitral valve repair: Comparison of new transthoracic 3D techniques to 2D transoesophageal echocardiography in the localization of mitral valve prolapse. Int J Cardiovasc Imaging, 2018, 34(7): 1099-1107.
23.	Garg P, Swift AJ, Zhong L, et al. Assessment of mitral valve regurgitation by cardiovascular magnetic resonance imaging. Nat Rev Cardiol, 2020, 17(5): 298-312.
24.	Durst R, Sauls K, Peal DS, et al. Mutations in DCHS1 cause mitral valve prolapse. Nature, 2015, 525(7567): 109-113.
25.	Oda H, Sato T, Kunishima S, et al. Exon skipping causes atypical phenotypes associated with a loss-of-function mutation in FLNA by restoring its protein function. Eur J Hum Genet, 2016, 24(3): 408-414.
26.	Vanem TT, Geiran OR, Krohg-Sørensen K, et al. Survival, causes of death, and cardiovascular events in patients with Marfan syndrome. Mol Genet Genomic Med, 2018, 6(6): 1114-1123.
27.	Mühlstädt K, De Backer J, von Kodolitsch Y, et al. Case-matched comparison of cardiovascular outcome in Loeys-Dietz syndrome versus Marfan syndrome. J Clin Med, 2019, 8(12): 2079.
28.	Morningstar JE, Nieman A, Wang C, et al. Mitral valve prolapse and its motley crew-syndromic prevalence, pathophysiology, and progression of a common heart condition. J Am Heart Assoc, 2021, 10(13): e020919.
29.	Robinson PN, Arteaga-Solis E, Baldock C, et al. The molecular genetics of Marfan syndrome and related disorders. J Med Genet, 2006, 43(10): 769-787.
30.	Sakai LY, Keene DR, Renard M, et al. FBN1: The disease-causing gene for Marfan syndrome and other genetic disorders. Gene, 2016, 591(1): 279-291.
31.	Gong B, Yang L, Wang Q, et al. Mutation screening in the FBN1 gene responsible for Marfan syndrome and related disorder in Chinese families. Mol Genet Genomic Med, 2019, 7(4): e00594.
32.	De Cario R, Sticchi E, Lucarini L, et al. Role of TGFBR1 and TGFBR2 genetic variants in Marfan syndrome. J Vasc Surg, 2018, 68(1): 225-233.
33.	Bitarafan F, Razmara E, Khodaeian M, et al. Three novel variants identified in FBN1 and TGFBR2 in seven Iranian families with suspected Marfan syndrome. Mol Genet Genomic Med, 2020, 8(8): e1274.
34.	Attias D, Stheneur C, Roy C, et al. Comparison of clinical presentations and outcomes between patients with TGFBR2 and FBN1 mutations in Marfan syndrome and related disorders. Circulation, 2009, 120(25): 2541-2549.
35.	Milewicz DM, Braverman AC, De Backer J, et al. Marfan syndrome. Nat Rev Dis Primers, 2021, 7(1): 64.
36.	Ramirez F, Caescu C, Wondimu E, et al. Marfan syndrome; A connective tissue disease at the crossroads of mechanotransduction, TGFβ signaling and cell stemness. Matrix Biol, 2018, 71-72: 82-89.
37.	van Andel MM, Indrakusuma R, Jalalzadeh H, et al. Long-term clinical outcomes of losartan in patients with Marfan syndrome: Follow-up of the multicentre randomized controlled COMPARE trial. Eur Heart J, 2020, 41(43): 4181-4187.
38.	Camerota L, Ritelli M, Wischmeijer A, et al. Genotypic categorization of Loeys-Dietz syndrome based on 24 novel families and literature data. Genes (Basel), 2019, 10(10): 764.
39.	Luo X, Deng S, Jiang Y, et al. Identification of a pathogenic TGFBR2 variant in a patient with Loeys-Dietz syndrome. Front Genet, 2020, 11: 479.
40.	Courtois A, Coppieters W, Bours V, et al. A novel SMAD3 mutation caused multiple aneurysms in a patient without osteoarthritis symptoms. Eur J Med Genet, 2017, 60(4): 228-231.
41.	Trochu JN, Kyndt F, Schott JJ, et al. Clinical characteristics of a familial inherited myxomatous valvular dystrophy mapped to Xq28. J Am Coll Cardiol, 2000, 35(7): 1890-1897.
42.	Popa MO, Irimia AM, Papagheorghe MN, et al. The mechanisms, diagnosis and management of mitral regurgitation in mitral valve prolapse and hypertrophic cardiomyopathy. Discoveries (Craiova), 2016, 4(2): e61.
43.	Kyndt F, Gueffet JP, Probst V, et al. Mutations in the gene encoding filamin A as a cause for familial cardiac valvular dystrophy. Circulation, 2007, 115(1): 40-49.
44.	Ritelli M, Morlino S, Giacopuzzi E, et al. Ehlers-Danlos syndrome with lethal cardiac valvular dystrophy in males carrying a novel splice mutation in FLNA. Am J Med Genet A, 2017, 173(1): 169-176.
45.	Mercer CL, Andreoletti G, Carroll A, et al. Familial ebstein anomaly: Whole exome sequencing identifies novel phenotype associated with FLNA. Circ Cardiovasc Genet, 2017, 10(6): e001683.
46.	Dina C, Bouatia-Naji N, Tucker N, et al. Genetic association analyses highlight biological pathways underlying mitral valve prolapse. Nat Genet, 2015, 47(10): 1206-1211.
47.	Dye B, Lincoln J. The endocardium and heart valves. Cold Spring Harb Perspect Biol, 2020, 12(12): a036723.
48.	Poelmann RE, Gittenberger-de Groot AC. Hemodynamics in cardiac development. J Cardiovasc Dev Dis, 2018, 5(4): 54.
49.	Chakrabarti M, Al-Sammarraie N, Gebere MG, et al. Transforming growth factor Beta3 is required for cardiovascular development. J Cardiovasc Dev Dis, 2020, 7(2): 19.
50.	Ma M, Li P, Shen H, et al. Dysregulated endocardial TGFβ signaling and mesenchymal transformation result in heart outflow tract septation failure. Dev Biol, 2016, 409(1): 272-276.
51.	Dituri F, Cossu C, Mancarella S, et al. The interactivity between TGFβ and BMP signaling in organogenesis, fibrosis, and cancer. Cells, 2019, 8(10): 1130.
52.	Beets K, Staring MW, Criem N, et al. BMP-SMAD signalling output is highly regionalized in cardiovascular and lymphatic endothelial networks. BMC Dev Biol, 2016, 16(1): 34.
53.	Gomez-Puerto MC, Iyengar PV, García de Vinuesa A, et al. Bone morphogenetic protein receptor signal transduction in human disease. J Pathol, 2019, 247(1): 9-20.
54.	Yang J, Mishina Y. Generation and identification of genetically modified mice for BMP receptors. Methods Mol Biol, 2019, 1891: 165-177.
55.	Tallquist MD, Soriano P. Epiblast-restricted Cre expression in MORE mice: A tool to distinguish embryonic vs. extra-embryonic gene function. Genesis, 2000, 26(2): 113-115.

1. Delling FN, Vasan RS. Epidemiology and pathophysiology of mitral valve prolapse: New insights into disease progression, genetics, and molecular basis. Circulation, 2014, 129(21): 2158-2170.
2. Delling FN, Rong J, Larson MG, et al. Evolution of mitral valve prolapse: Insights from the Framingham heart study. Circulation, 2016, 133(17): 1688-1695.
3. van Wijngaarden AL, Kruithof BPT, Vinella T, et al. Characterization of degenerative mitral valve disease: Differences between fibroelastic deficiency and Barlow's disease. J Cardiovasc Dev Dis, 2021, 8(2): 23.
4. Hjortnaes J, Keegan J, Bruneval P, et al. Comparative histopathological analysis of mitral valves in Barlow disease and fibroelastic deficiency. Semin Thorac Cardiovasc Surg, 2016, 28(4): 757-767.
5. Hei S, Iwataki M, Jang JY, et al. Relations of augmented systolic annular expansion and leaflet/papillary muscle dynamics in late-systolic mitral valve prolapse evaluated by echocardiography with a speckle tracking analysis. Int Heart J, 2020, 61(5): 970-978.
6. Parwani P, Avierinos JF, Levine RA, et al. Mitral valve prolapse: Multimodality imaging and genetic insights. Prog Cardiovasc Dis, 2017, 60(3): 361-369.
7. Freed LA, Levy D, Levine RA, et al. Prevalence and clinical outcome of mitral-valve prolapse. N Engl J Med, 1999, 341(1): 1-7.
8. Perazzolo Marra M, Basso C. Mechanical dispersion and arrhythmic mitral valve prolapse: Aubstrate and trigger in electrical instability. Heart, 2019, 105(14): 1053-1054.
9. Dziadzko V, Clavel MA, Dziadzko M, et al. Outcome and undertreatment of mitral regurgitation: A community cohort study. Lancet, 2018, 391(10124): 960-969.
10. Meester JAN, Verstraeten A, Schepers D, et al. Differences in manifestations of Marfan syndrome, Ehlers-Danlos syndrome, and Loeys-Dietz syndrome. Ann Cardiothorac Surg, 2017, 6(6): 582-594.
11. Spartalis M, Tzatzaki E, Spartalis E, et al. Mitral valve prolapse: An underestimated cause of sudden cardiac death—A current review of the literature. J Thorac Dis, 2017, 9(12): 5390-5398.
12. Thacoor A. Mitral valve prolapse and Marfan syndrome. Congenit Heart Dis, 2017, 12(4): 430-434.
13. Gasser S, Reichenspurner H, Girdauskas E. Genomic analysis in patients with myxomatous mitral valve prolapse: Current state of knowledge. BMC Cardiovasc Disord, 2018, 18(1): 41.
14. Freed LA, Benjamin EJ, Levy D, et al. Mitral valve prolapse in the general population: The benign nature of echocardiographic features in the Framingham Heart Study. J Am Coll Cardiol, 2002, 40(7): 1298-1304.
15. Disse S, Abergel E, Berrebi A, et al. Mapping of a first locus for autosomal dominant myxomatous mitral-valve prolapse to chromosome 16p11. 2-p12. 1. Am J Hum Genet, 1999, 65(5): 1242-1251.
16. Freed LA, Acierno JS, Dai D, et al. A locus for autosomal dominant mitral valve prolapse on chromosome 11p15. 4. Am J Hum Genet, 2003, 72(6): 1551-1559.
17. Nesta F, Leyne M, Yosefy C, et al. New locus for autosomal dominant mitral valve prolapse on chromosome 13: Clinical insights from genetic studies. Circulation, 2005, 112(13): 2022-2030.
18. Le Tourneau T, Le Scouarnec S, Cueff C, et al. New insights into mitral valve dystrophy: A Filamin-A genotype-phenotype and outcome study. Eur Heart J, 2018, 39(15): 1269-1277.
19. Kim KJ, Kim HK, Park JB, et al. Transthoracic echocardiographic findings of mitral regurgitation caused by commissural prolapse. JACC Cardiovasc Imaging, 2018, 11(6): 925-926.
20. Militaru S, Bonnefous O, Hami K, et al. Validation of semiautomated quantification of mitral valve regurgitation by three-dimensional color Doppler transesophageal echocardiography. J Am Soc Echocardiogr, 2020, 33(3): 342-354.
21. Berdejo J, Shiota M, Mihara H, et al. Vena contracta analysis by color Doppler three-dimensional transesophageal echocardiography shows geometrical differences between prolapse and pseudoprolapse in eccentric mitral regurgitation. Echocardiography, 2017, 34(5): 683-689.
22. Gripari P, Mapelli M, Bellacosa I, et al. Transthoracic echocardiography in patients undergoing mitral valve repair: Comparison of new transthoracic 3D techniques to 2D transoesophageal echocardiography in the localization of mitral valve prolapse. Int J Cardiovasc Imaging, 2018, 34(7): 1099-1107.
23. Garg P, Swift AJ, Zhong L, et al. Assessment of mitral valve regurgitation by cardiovascular magnetic resonance imaging. Nat Rev Cardiol, 2020, 17(5): 298-312.
24. Durst R, Sauls K, Peal DS, et al. Mutations in DCHS1 cause mitral valve prolapse. Nature, 2015, 525(7567): 109-113.
25. Oda H, Sato T, Kunishima S, et al. Exon skipping causes atypical phenotypes associated with a loss-of-function mutation in FLNA by restoring its protein function. Eur J Hum Genet, 2016, 24(3): 408-414.
26. Vanem TT, Geiran OR, Krohg-Sørensen K, et al. Survival, causes of death, and cardiovascular events in patients with Marfan syndrome. Mol Genet Genomic Med, 2018, 6(6): 1114-1123.
27. Mühlstädt K, De Backer J, von Kodolitsch Y, et al. Case-matched comparison of cardiovascular outcome in Loeys-Dietz syndrome versus Marfan syndrome. J Clin Med, 2019, 8(12): 2079.
28. Morningstar JE, Nieman A, Wang C, et al. Mitral valve prolapse and its motley crew-syndromic prevalence, pathophysiology, and progression of a common heart condition. J Am Heart Assoc, 2021, 10(13): e020919.
29. Robinson PN, Arteaga-Solis E, Baldock C, et al. The molecular genetics of Marfan syndrome and related disorders. J Med Genet, 2006, 43(10): 769-787.
30. Sakai LY, Keene DR, Renard M, et al. FBN1: The disease-causing gene for Marfan syndrome and other genetic disorders. Gene, 2016, 591(1): 279-291.
31. Gong B, Yang L, Wang Q, et al. Mutation screening in the FBN1 gene responsible for Marfan syndrome and related disorder in Chinese families. Mol Genet Genomic Med, 2019, 7(4): e00594.
32. De Cario R, Sticchi E, Lucarini L, et al. Role of TGFBR1 and TGFBR2 genetic variants in Marfan syndrome. J Vasc Surg, 2018, 68(1): 225-233.
33. Bitarafan F, Razmara E, Khodaeian M, et al. Three novel variants identified in FBN1 and TGFBR2 in seven Iranian families with suspected Marfan syndrome. Mol Genet Genomic Med, 2020, 8(8): e1274.
34. Attias D, Stheneur C, Roy C, et al. Comparison of clinical presentations and outcomes between patients with TGFBR2 and FBN1 mutations in Marfan syndrome and related disorders. Circulation, 2009, 120(25): 2541-2549.
35. Milewicz DM, Braverman AC, De Backer J, et al. Marfan syndrome. Nat Rev Dis Primers, 2021, 7(1): 64.
36. Ramirez F, Caescu C, Wondimu E, et al. Marfan syndrome; A connective tissue disease at the crossroads of mechanotransduction, TGFβ signaling and cell stemness. Matrix Biol, 2018, 71-72: 82-89.
37. van Andel MM, Indrakusuma R, Jalalzadeh H, et al. Long-term clinical outcomes of losartan in patients with Marfan syndrome: Follow-up of the multicentre randomized controlled COMPARE trial. Eur Heart J, 2020, 41(43): 4181-4187.
38. Camerota L, Ritelli M, Wischmeijer A, et al. Genotypic categorization of Loeys-Dietz syndrome based on 24 novel families and literature data. Genes (Basel), 2019, 10(10): 764.
39. Luo X, Deng S, Jiang Y, et al. Identification of a pathogenic TGFBR2 variant in a patient with Loeys-Dietz syndrome. Front Genet, 2020, 11: 479.
40. Courtois A, Coppieters W, Bours V, et al. A novel SMAD3 mutation caused multiple aneurysms in a patient without osteoarthritis symptoms. Eur J Med Genet, 2017, 60(4): 228-231.
41. Trochu JN, Kyndt F, Schott JJ, et al. Clinical characteristics of a familial inherited myxomatous valvular dystrophy mapped to Xq28. J Am Coll Cardiol, 2000, 35(7): 1890-1897.
42. Popa MO, Irimia AM, Papagheorghe MN, et al. The mechanisms, diagnosis and management of mitral regurgitation in mitral valve prolapse and hypertrophic cardiomyopathy. Discoveries (Craiova), 2016, 4(2): e61.
43. Kyndt F, Gueffet JP, Probst V, et al. Mutations in the gene encoding filamin A as a cause for familial cardiac valvular dystrophy. Circulation, 2007, 115(1): 40-49.
44. Ritelli M, Morlino S, Giacopuzzi E, et al. Ehlers-Danlos syndrome with lethal cardiac valvular dystrophy in males carrying a novel splice mutation in FLNA. Am J Med Genet A, 2017, 173(1): 169-176.
45. Mercer CL, Andreoletti G, Carroll A, et al. Familial ebstein anomaly: Whole exome sequencing identifies novel phenotype associated with FLNA. Circ Cardiovasc Genet, 2017, 10(6): e001683.
46. Dina C, Bouatia-Naji N, Tucker N, et al. Genetic association analyses highlight biological pathways underlying mitral valve prolapse. Nat Genet, 2015, 47(10): 1206-1211.
47. Dye B, Lincoln J. The endocardium and heart valves. Cold Spring Harb Perspect Biol, 2020, 12(12): a036723.
48. Poelmann RE, Gittenberger-de Groot AC. Hemodynamics in cardiac development. J Cardiovasc Dev Dis, 2018, 5(4): 54.
49. Chakrabarti M, Al-Sammarraie N, Gebere MG, et al. Transforming growth factor Beta3 is required for cardiovascular development. J Cardiovasc Dev Dis, 2020, 7(2): 19.
50. Ma M, Li P, Shen H, et al. Dysregulated endocardial TGFβ signaling and mesenchymal transformation result in heart outflow tract septation failure. Dev Biol, 2016, 409(1): 272-276.
51. Dituri F, Cossu C, Mancarella S, et al. The interactivity between TGFβ and BMP signaling in organogenesis, fibrosis, and cancer. Cells, 2019, 8(10): 1130.
52. Beets K, Staring MW, Criem N, et al. BMP-SMAD signalling output is highly regionalized in cardiovascular and lymphatic endothelial networks. BMC Dev Biol, 2016, 16(1): 34.
53. Gomez-Puerto MC, Iyengar PV, García de Vinuesa A, et al. Bone morphogenetic protein receptor signal transduction in human disease. J Pathol, 2019, 247(1): 9-20.
54. Yang J, Mishina Y. Generation and identification of genetically modified mice for BMP receptors. Methods Mol Biol, 2019, 1891: 165-177.
55. Tallquist MD, Soriano P. Epiblast-restricted Cre expression in MORE mice: A tool to distinguish embryonic vs. extra-embryonic gene function. Genesis, 2000, 26(2): 113-115.

Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Research progress of syndromic and non-syndromic mitral valve prolapse and its genetics

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