Figure 1.
Characterization of 16p13.1 duplications in individuals with thoracic aortic aneurysms and dissections.
(A) The extent of 16p13.1 duplications in controls (green), the discovery cohort (blue) and the replication cohort (black) is shown. The scale is in megabases. The common duplicated region that is spanned by all CNVs is boxed. Below is a schematic of the 16p13.1-p12.3 region, which includes the location of genes and low-copy repeats (LCR, arrows).
Table 1.
Frequency of 16p13 duplications in cases and controls.
Table 2.
Clinical characteristics of patients with 16p13.1 duplications.
Figure 2.
Segregation of the 16p13.1 chromosomal duplication in patients with familial inheritance of thoracic aortic aneurysms and dissections.
Circles indicate females; squares indicate males. Pedigrees of families TAA337 and TAA499 are shown, and the legend indicates the diseases and the presence or absence of the 16p13.1 duplication in the family members.
Figure 3.
Pathological abnormalities and MYH11 expression levels in aortic tissue associated with 16p13.1 duplication in patients with staad.
(A) Movat staining of aortic media from a 16p13.1 duplication patient shows medial degeneration characterized by proteoglycan accumulation (stained blue), loss and fragmentation of elastic fibers (stained black) and an acute aortic dissection (arrowhead) when compared with a control aorta. Some of the arteries in the vasa vasorum of the patients with 16p13.1 duplication showed increased size and thickness (arrows). Smooth muscle cell (SMC) alpha-actin staining of the vasa vasorum indicated that increased thickness of vasa vasorum was due to increased SMCs in the medial layer. (B) Quantitative real-time PCR assays (Q-PCR) of MYH11 expression levels in ascending aortic tissues from STAAD patients with and without 16p13.1 duplications and control aortic tissues indicated that MYH11 message levels were significantly increased in patients with 16p13.1 duplication (n = 4), compared to those of patients without 16p13.1 duplication (n = 6) or to controls (n = 5). The relative MYH11 mRNA expression was determined by Q-PCR and normalized to either calponin-1 (CNN1) or GAPDH.