Mutations in myosin heavy chain 11 cause a syndrome associating thoracic aortic aneurysm/aortic dissection and patent ductus arteriosus.

Limin Zhu; Roger Vranckx; Philippe Khau van Kien; Alain Lalande; Nicolas Boisset; Flavie Mathieu; Mark Wegman; Luke Glancy; Jean-Marie Gasc; François Brunotte; Patrick Bruneval; Jean-Eric Wolf; Jean-Baptiste Michel; Xavier Jeunemaitre

Mutations in myosin heavy chain 11 cause a syndrome associating thoracic aortic aneurysm/aortic dissection and patent ductus arteriosus.

Limin Zhu ^{1, 2, 3, 4} Roger Vranckx ^{5, 6} Philippe Khau van Kien ^{1, 7, 8} Alain Lalande ^{9, 10} Nicolas Boisset ¹¹ Flavie Mathieu ^{2, 3} Mark Wegman ¹² Luke Glancy ¹² Jean-Marie Gasc ^{2, 3} François Brunotte ^{9, 10} Patrick Bruneval ^{13, 14} Jean-Eric Wolf ^{7, 8} Jean-Baptiste Michel ^{5, 6} Xavier Jeunemaitre ^{1, 2, 3, 14}

1 Service de génétique [CHU HEGP]

2 Pathologie vasculaire et endocrinologie rénale

3 CDF - Collège de France

4 Ruijin Hospital, French Chinese Genomic Pole

5 LBPC - Hémostase, bio-ingénierie et remodelage cardiovasculaires

6 Faculté de Médecine Xavier Bichat

7 LPPCE - Laboratoire de Physiopathologie et de Pharmacologie Cardiovasculaire Expérimentale

8 Service de Cardiologie II, Centre Hospitalier Universitaire

9 Centre d'Imagerie par Résonance Magnétique, Centre Hospitalier Universitaire

10 Le2i - Laboratoire Electronique, Informatique et Image [UMR6303]

11 IMPMC - Institut de minéralogie et de physique des milieux condensés

12 Section of Cardiology, Department of Medicine

13 Service d'anatomo-pathologie [CHU HEGP]

14 UPD5 Médecine - Université Paris Descartes - Faculté de Médecine

Abstract : We have recently described two kindreds presenting thoracic aortic aneurysm and/or aortic dissection (TAAD) and patent ductus arteriosus (PDA)1, 2 and mapped the disease locus to 16p12.2-p13.13 (ref. 3). We now demonstrate that the disease is caused by mutations in the MYH11 gene affecting the C-terminal coiled-coil region of the smooth muscle myosin heavy chain, a specific contractile protein of smooth muscle cells (SMC). All individuals bearing the heterozygous mutations, even if asymptomatic, showed marked aortic stiffness. Examination of pathological aortas showed large areas of medial degeneration with very low SMC content. Abnormal immunological recognition of SM-MHC and the colocalization of wild-type and mutant rod proteins in SMC, in conjunction with differences in their coimmunoprecipitation capacities, strongly suggest a dominant-negative effect. Human MYH11 gene mutations provide the first example of a direct change in a specific SMC protein leading to an inherited arterial disease.

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Journal articles

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https://hal.archives-ouvertes.fr/hal-00022553
Contributor : Sylvia Deplanque <>
Submitted on : Tuesday, April 11, 2006 - 11:33:36 AM
Last modification on : Thursday, September 5, 2019 - 4:47:20 PM

Mutations in myosin heavy chain 11 cause a syndrome associating thoracic aortic aneurysm/aortic dissection and patent ductus arteriosus.

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Mutations in myosin heavy chain 11 cause a syndrome associating thoracic aortic aneurysm/aortic dissection and patent ductus arteriosus.

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