Analysis of multigenerational families with thoracic aortic aneurysms and dissections due to TGFBR1 or TGFBR2 mutations

V. Tran-Fadulu, H. Pannu, D. H. Kim, G. W. Vick, C. M. Lonsford, A. L. Lafont, C. Boccalandro, S. Smart, K. L. Peterson, J. Zenger Hain, M. C. Willing, J. S. Coselli, S. A. LeMaire, C. Ahn, P. H. Byers, D. M. Milewicz

Research output: Contribution to journalArticle

107 Citations (Scopus)

Abstract

Background: Mutations in the transforming growth factor β receptor type I and II genes (TGFBR1 and TGFBR2) cause Loeys-Dietz syndrome (LDS), characterised by thoracic aortic aneurysms and dissections (TAAD), aneurysms and dissections of other arteries, craniosynostosis, cleft palate/bifid uvula, hypertelorism, congenital heart defects, arterial tortuosity, and mental retardation. TGFBR2 mutations can also cause TAAD in the absence of features of LDS in large multigenerational families, yet only sporadic LDS cases or parent-child pairs with TGFBR1 mutations have been reported to date. Methods: The authors identified TGFBR1 missense mutations in multigenerational families with TAAD by DNA sequencing. Clinical features of affected individuals were assessed and compared with clinical features of previously described TGFBR2 families. Results: Statistical analyses of the clinical features of the TGFBR1 cohort (n = 30) were compared with clinical features of TGFBR2 cohort (n = 77). Significant differences were identified in clinical presentation and survival based on gender in TGFBR1 families but not in TGFBR2 families. In families with TGFBR1 mutations, men died younger than women based on Kaplan-Meier survival curves. In addition, men presented with TAAD and women often presented with dissections and aneurysms of arteries other than the ascending thoracic aorta. The data also suggest that individuals with TGFBR2 mutations are more likely to dissect at aortic diameters <5.0 cm than individuals with TGFBR1 mutations. Conclusion: This study is the first to demonstrate clinical differences between patients with TGFBR1 and TGFBR2 mutations. These differences are important for the clinical management and outcome of vascular diseases in these patients.

Original languageEnglish (US)
Pages (from-to)607-613
Number of pages7
JournalJournal of Medical Genetics
Volume46
Issue number9
DOIs
StatePublished - Sep 2009

Fingerprint

Thoracic Aortic Aneurysm
Dissection
Loeys-Dietz Syndrome
Mutation
Aneurysm
Arteries
Uvula
Hypertelorism
Craniosynostoses
Growth Factor Receptors
Congenital Heart Defects
Kaplan-Meier Estimate
Cleft Palate
Transforming Growth Factors
Missense Mutation
Thoracic Aorta
DNA Sequence Analysis
Vascular Diseases
Intellectual Disability
Aorta

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Tran-Fadulu, V., Pannu, H., Kim, D. H., Vick, G. W., Lonsford, C. M., Lafont, A. L., ... Milewicz, D. M. (2009). Analysis of multigenerational families with thoracic aortic aneurysms and dissections due to TGFBR1 or TGFBR2 mutations. Journal of Medical Genetics, 46(9), 607-613. https://doi.org/10.1136/jmg.2008.062844

Analysis of multigenerational families with thoracic aortic aneurysms and dissections due to TGFBR1 or TGFBR2 mutations. / Tran-Fadulu, V.; Pannu, H.; Kim, D. H.; Vick, G. W.; Lonsford, C. M.; Lafont, A. L.; Boccalandro, C.; Smart, S.; Peterson, K. L.; Zenger Hain, J.; Willing, M. C.; Coselli, J. S.; LeMaire, S. A.; Ahn, C.; Byers, P. H.; Milewicz, D. M.

In: Journal of Medical Genetics, Vol. 46, No. 9, 09.2009, p. 607-613.

Research output: Contribution to journalArticle

Tran-Fadulu, V, Pannu, H, Kim, DH, Vick, GW, Lonsford, CM, Lafont, AL, Boccalandro, C, Smart, S, Peterson, KL, Zenger Hain, J, Willing, MC, Coselli, JS, LeMaire, SA, Ahn, C, Byers, PH & Milewicz, DM 2009, 'Analysis of multigenerational families with thoracic aortic aneurysms and dissections due to TGFBR1 or TGFBR2 mutations', Journal of Medical Genetics, vol. 46, no. 9, pp. 607-613. https://doi.org/10.1136/jmg.2008.062844
Tran-Fadulu, V. ; Pannu, H. ; Kim, D. H. ; Vick, G. W. ; Lonsford, C. M. ; Lafont, A. L. ; Boccalandro, C. ; Smart, S. ; Peterson, K. L. ; Zenger Hain, J. ; Willing, M. C. ; Coselli, J. S. ; LeMaire, S. A. ; Ahn, C. ; Byers, P. H. ; Milewicz, D. M. / Analysis of multigenerational families with thoracic aortic aneurysms and dissections due to TGFBR1 or TGFBR2 mutations. In: Journal of Medical Genetics. 2009 ; Vol. 46, No. 9. pp. 607-613.
@article{d4a79b1eec4549879cb6054b2409e6b6,
title = "Analysis of multigenerational families with thoracic aortic aneurysms and dissections due to TGFBR1 or TGFBR2 mutations",
abstract = "Background: Mutations in the transforming growth factor β receptor type I and II genes (TGFBR1 and TGFBR2) cause Loeys-Dietz syndrome (LDS), characterised by thoracic aortic aneurysms and dissections (TAAD), aneurysms and dissections of other arteries, craniosynostosis, cleft palate/bifid uvula, hypertelorism, congenital heart defects, arterial tortuosity, and mental retardation. TGFBR2 mutations can also cause TAAD in the absence of features of LDS in large multigenerational families, yet only sporadic LDS cases or parent-child pairs with TGFBR1 mutations have been reported to date. Methods: The authors identified TGFBR1 missense mutations in multigenerational families with TAAD by DNA sequencing. Clinical features of affected individuals were assessed and compared with clinical features of previously described TGFBR2 families. Results: Statistical analyses of the clinical features of the TGFBR1 cohort (n = 30) were compared with clinical features of TGFBR2 cohort (n = 77). Significant differences were identified in clinical presentation and survival based on gender in TGFBR1 families but not in TGFBR2 families. In families with TGFBR1 mutations, men died younger than women based on Kaplan-Meier survival curves. In addition, men presented with TAAD and women often presented with dissections and aneurysms of arteries other than the ascending thoracic aorta. The data also suggest that individuals with TGFBR2 mutations are more likely to dissect at aortic diameters <5.0 cm than individuals with TGFBR1 mutations. Conclusion: This study is the first to demonstrate clinical differences between patients with TGFBR1 and TGFBR2 mutations. These differences are important for the clinical management and outcome of vascular diseases in these patients.",
author = "V. Tran-Fadulu and H. Pannu and Kim, {D. H.} and Vick, {G. W.} and Lonsford, {C. M.} and Lafont, {A. L.} and C. Boccalandro and S. Smart and Peterson, {K. L.} and {Zenger Hain}, J. and Willing, {M. C.} and Coselli, {J. S.} and LeMaire, {S. A.} and C. Ahn and Byers, {P. H.} and Milewicz, {D. M.}",
year = "2009",
month = "9",
doi = "10.1136/jmg.2008.062844",
language = "English (US)",
volume = "46",
pages = "607--613",
journal = "Journal of Medical Genetics",
issn = "0022-2593",
publisher = "BMJ Publishing Group",
number = "9",

}

TY - JOUR

T1 - Analysis of multigenerational families with thoracic aortic aneurysms and dissections due to TGFBR1 or TGFBR2 mutations

AU - Tran-Fadulu, V.

AU - Pannu, H.

AU - Kim, D. H.

AU - Vick, G. W.

AU - Lonsford, C. M.

AU - Lafont, A. L.

AU - Boccalandro, C.

AU - Smart, S.

AU - Peterson, K. L.

AU - Zenger Hain, J.

AU - Willing, M. C.

AU - Coselli, J. S.

AU - LeMaire, S. A.

AU - Ahn, C.

AU - Byers, P. H.

AU - Milewicz, D. M.

PY - 2009/9

Y1 - 2009/9

N2 - Background: Mutations in the transforming growth factor β receptor type I and II genes (TGFBR1 and TGFBR2) cause Loeys-Dietz syndrome (LDS), characterised by thoracic aortic aneurysms and dissections (TAAD), aneurysms and dissections of other arteries, craniosynostosis, cleft palate/bifid uvula, hypertelorism, congenital heart defects, arterial tortuosity, and mental retardation. TGFBR2 mutations can also cause TAAD in the absence of features of LDS in large multigenerational families, yet only sporadic LDS cases or parent-child pairs with TGFBR1 mutations have been reported to date. Methods: The authors identified TGFBR1 missense mutations in multigenerational families with TAAD by DNA sequencing. Clinical features of affected individuals were assessed and compared with clinical features of previously described TGFBR2 families. Results: Statistical analyses of the clinical features of the TGFBR1 cohort (n = 30) were compared with clinical features of TGFBR2 cohort (n = 77). Significant differences were identified in clinical presentation and survival based on gender in TGFBR1 families but not in TGFBR2 families. In families with TGFBR1 mutations, men died younger than women based on Kaplan-Meier survival curves. In addition, men presented with TAAD and women often presented with dissections and aneurysms of arteries other than the ascending thoracic aorta. The data also suggest that individuals with TGFBR2 mutations are more likely to dissect at aortic diameters <5.0 cm than individuals with TGFBR1 mutations. Conclusion: This study is the first to demonstrate clinical differences between patients with TGFBR1 and TGFBR2 mutations. These differences are important for the clinical management and outcome of vascular diseases in these patients.

AB - Background: Mutations in the transforming growth factor β receptor type I and II genes (TGFBR1 and TGFBR2) cause Loeys-Dietz syndrome (LDS), characterised by thoracic aortic aneurysms and dissections (TAAD), aneurysms and dissections of other arteries, craniosynostosis, cleft palate/bifid uvula, hypertelorism, congenital heart defects, arterial tortuosity, and mental retardation. TGFBR2 mutations can also cause TAAD in the absence of features of LDS in large multigenerational families, yet only sporadic LDS cases or parent-child pairs with TGFBR1 mutations have been reported to date. Methods: The authors identified TGFBR1 missense mutations in multigenerational families with TAAD by DNA sequencing. Clinical features of affected individuals were assessed and compared with clinical features of previously described TGFBR2 families. Results: Statistical analyses of the clinical features of the TGFBR1 cohort (n = 30) were compared with clinical features of TGFBR2 cohort (n = 77). Significant differences were identified in clinical presentation and survival based on gender in TGFBR1 families but not in TGFBR2 families. In families with TGFBR1 mutations, men died younger than women based on Kaplan-Meier survival curves. In addition, men presented with TAAD and women often presented with dissections and aneurysms of arteries other than the ascending thoracic aorta. The data also suggest that individuals with TGFBR2 mutations are more likely to dissect at aortic diameters <5.0 cm than individuals with TGFBR1 mutations. Conclusion: This study is the first to demonstrate clinical differences between patients with TGFBR1 and TGFBR2 mutations. These differences are important for the clinical management and outcome of vascular diseases in these patients.

UR - http://www.scopus.com/inward/record.url?scp=69749113581&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=69749113581&partnerID=8YFLogxK

U2 - 10.1136/jmg.2008.062844

DO - 10.1136/jmg.2008.062844

M3 - Article

C2 - 19542084

AN - SCOPUS:69749113581

VL - 46

SP - 607

EP - 613

JO - Journal of Medical Genetics

JF - Journal of Medical Genetics

SN - 0022-2593

IS - 9

ER -