Acute Aortic Disease.. - Index of

Genetic Basis of Thoracic Aortic Aneurysms 113
familial TAAD, accounting for approximately 5% of familial TAAD (95% CI:
1.4–12.3%) (46,47). Although the majority of vascular disease in families with
TGFBR2 mutations involved ascending aortic aneurysms (leading to type A dissections),
affected family members also had descending aortic disease and aneurysms
of arteries in other vascular beds, including cerebral, carotid, and popliteal
aneurysms (Fig. 8).
A striking finding in the mutational analysis was that all four families
carried mutations that affected arginine at amino acid 460 in the intracellular
domain of TGFBR2, suggesting a mutation “hot-spot” or familial TAAD and
establishing a strong genotype–phenotype correlation between familial TAAD
and mutations at this location. Polymorphic markers flanking the TGFBR2 mutation
indicated that the families do not share a common haplotype, an observation
consistent with these mutations occurring independently and providing further
evidence for a “hot spot” for mutations causing this disease.
d. 57
d.37
III:1 III:2 III:3III:4 III:5 III:6 III:7 III:8 III:9 III:10 III:11 III:12 III:13 III:13III:14III:15III:16
III:14 III:15 III:16 III:17 III:18 III:19 III:19III:20 III:20 III:21 III:22 III:23 III:24 III:25 III:26 III:27 III:27III:28
III:28 III:29 III:30 III:31 III:31III:32 III:32 III:33III:34 III:33 III:34 III:35
d. 19
IV:1 IV:2 IV:2 IV:3 IV:4 IV:5 IV:6 IV:7 IV:8 IV:9 IV:10 IV:11 IV:12IV:13 IV:12 IV:13 IV:14 IV:15 IV:16
VI:1
TAA 035
17
IV:1
3
VI:2 VI:3
IV:2
d. 72
II:1
V:1 V:2 V:3 V:4 V:5 V:6
TAA 150
TAA 067
II:2
V:7 V:8
d.49
III:1 III:2
d.46
d.46 71 y
IV:3 IV:4 IV:5 IV:6 IV:7
II:1 II:2
IV:8 IV:9
d.54
d.27
IV:10 IV:11 IV:12
d. 22
3 6
2
3
V:1 V:2 V:3 V:4 V:5 V:6 V:7 V:8 V:9 V:10V:11 V:12V:13V:14
V:15 V:16 V:17 V:18 V:19 V:20 V:21 V:22 V:23V:24
VI:4 VI:5
2
VI:6
VI:7
I:1 I:2
II:3
d. 40's
d.39
d.39
III:3
2
III:4 III:5 III:6 III:7 III:4 III:7 III:5 III:8
d.53
IV:13
19 16 dx.20
2
7 9
VI:8 VI:9 VI:10 VI:11 VI:12 VI:13 VI:14 VI:15
d.30's
I:1
I:2
d.88 d.40's
d.77
II:2 II:3
II:4 II:5
d.76
d.72
d.48
d.54
III:4
III:5
III:6 III:7 III:8 III:9
d.51
d.51
2 2 3
IV:1 IV:2 IV:3 IV:4 IV:5 IV:6
IV:7 IV:8 IV:11 IV:16 IV:18
d.31
V:1 V:2 V:3 V:4 V:5 V:6 V:7
3
V:8 V:9 V:10 V:11 V:12 V:13 V:14 V:15
2 3
11 7
2 3
VI:1 VI:2 VI:3 VI:4 VI:5
VI:6 VI:7 VI:8
4
IV:14 IV:15 IV:16IV:17
IV:17IV:18IV:18
IV:19 IV:19 IV:20IV:21
IV:20
Figure 8 Pedigrees of thoracic aortic aneurysm and dissection families with TGFBR2
mutations. Vascular disease status is indicated as filled quadrant, with legend indicating vascular
disease associated with quadrant. Aneurysms of arteries in various vascular beds are
observed in affected individuals, along with des cending aortic disease. TGFBR2 was
sequenced from all family members providing samples for these studies. Dark gray symbols
indicate individuals heterozygous for TGFBR2 mutation 1378C→T (R460C). Light gray
symbols indicate individuals heterozygous for TGFBR2 mutation 1379G→A (R460H).
Medium gray symbols indicate individuals whose DNA was sequenced and who were found
not to have TGFBR2 mutation. Source: From Ref. 47.
V:25
d. 30's
I:1 I:2
d. 63
II:3 II:4 II:5
II:6 II:7
II:8
IV:17 IV:18 IV:19 IV:20
d.59 d.50’s
I:1 I:2
d.56 d.65
d.74 d.62 d.73
3
II:1 II:2 II:3 II:4 II:5 II:6 II:7 II:8 II:9 II:10 II:11 II:12 II:13
dx.68 dx.56
d.21
III:1 III:2 III:3 III:4 III:5 III:6 III:7 III:8 III:9
d. 30’s
dx.41
IV:1 IV:2 IV:3 IV:4 IV:5
3
IV:21
TAA 090
2
IV:22 IV:23 IV:24 IV:25 IV:26 IV:26 IV:27 IV:28 IV:28 IV:29 IV:30 IV:30IV:31 IV:31 IV:32 IV:33 IV:33 IV:34 IV:35 IV:35
II:9
= Ascending Aortic Aneurysm/Dissection
= Carotid Aneurysm/Dissection
= Descending Aortic Aneurysm/Dissection
= Cerebral Aneurysm
= Abdominal and Popliteal Aneurysm/Dissection
= TGFBR2 mutation 1379G A
= TGFBR2 mutation 1378C T
= No TGFBR2 mutation