Aortic Aneurysm, Familial Thoracic 7

A number sign (#) is used with this entry because of evidence that aortic dissection with or without aortic aneurysm can be caused by heterozygous mutation in the MYLK gene (600922).

For a general phenotypic description and discussion of genetic heterogeneity of thoracic aortic aneurysm, see AAT1 (607086).

Molecular Genetics

Wang et al. (2010) analyzed the MYLK gene in 193 probands from unrelated families in which 2 or more members had thoracic aortic aneurysms or dissections. They identified 2 heterozygous variants (600922.0001 and 600922.0002) that segregated with aortic dissections in 2 families, respectively, and were not found in 188 ethnically matched controls. Three additional MYLK variants were identified in 3 unrelated probands that were not detected in controls, but family members were not available for segregation analysis. Wang et al. (2010) noted that acute aortic dissections in the 2 mutation-positive families occurred with little to no aortic enlargement, suggesting that there were likely other family members with the defective gene who appeared phenotypically normal. Examination of ascending aortic tissue from 2 affected members of 1 family indicated medial degeneration of the aorta, characterized by increased proteoglycan deposition and mild elastic fiber thinning and fragmentation, along with a significant increase in the presence of small arteries in the medial layer of the aorta. Wang et al. (2010) noted that a similar increase of arteries in the medial layer had been described in patients with mutations in the MYH11 gene (160745) (see Pannu et al. (2007) and AAT4, 132900).