Analysis of multigenerational families with thoracic aortic aneurysms and dissections due to TGFBR1 or TGFBR2 mutations
| Autor: | Cristina Boccalandro, Dong H. Kim, J. Zenger Hain, A. L. Lafont, Hariyadarshi Pannu, Peter H. Byers, Dianna M. Milewicz, Chul Ahn, Van Tran-Fadulu, Scott A. LeMaire, Joseph S. Coselli, Marcia C. Willing, S. Smart, G. W. Vick, Kirk L. Peterson, C. M. Lonsford |
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| Rok vydání: | 2009 |
| Předmět: |
Adult
Male medicine.medical_specialty Adolescent Mutation Missense Receptor Transforming Growth Factor-beta Type I Kaplan-Meier Estimate Protein Serine-Threonine Kinases Magnetic resonance angiography Craniosynostosis Cohort Studies Aortic aneurysm Aneurysm medicine.artery Internal medicine Genetics medicine Humans Thoracic aorta Genetic Predisposition to Disease Hypertelorism Genetics (clinical) Family Health Aortic dissection Chi-Square Distribution Aortic Aneurysm Thoracic medicine.diagnostic_test Vascular disease business.industry Receptor Transforming Growth Factor-beta Type II Anatomy Middle Aged medicine.disease Pedigree Aortic Dissection Female medicine.symptom business Receptors Transforming Growth Factor beta Magnetic Resonance Angiography |
| Zdroj: | Journal of Medical Genetics. 46:607-613 |
| ISSN: | 1468-6244 0022-2593 |
| DOI: | 10.1136/jmg.2008.062844 |
| Popis: | 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 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. |
| Databáze: | OpenAIRE |
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