Mutations in myosin heavy chain 11 cause a syndrome associating thoracic aortic aneurysm/aortic dissection and patent ductus arteriosus
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 colocal…
Familial thoracic aortic aneurysm/dissection with patent ductus arteriosus: genetic arguments for a particular pathophysiological entity.
International audience; Thoracic aortic aneurysm and aortic dissection (TAA and AD) are an important cause of sudden death. Familial cases could account for 20% of all cases. A genetic heterogeneity with two identified genes (FBN1 and COL3A1) and three loci (3p24-25 or MFS2/TAAD2, 5q13-q14 and 11q23.2-24) has been shown previously. Study of a single family composed of 179 members with an abnormally high occurrence of TAA/AD disease. A total of 40 subjects from three generations were investigated. In addition to five cases of stroke and three cases of sudden death, there were four cases of AD and four cases of TAA in adults. In all, 11 cases of patent ductus arteriosus (PDA) were observed, t…