Analysis of multigenerational families with thoracic aortic aneurysms and dissections due to TGFBR1 or TGFBR2 mutations
ABSTRACT Mutations in the transforming growth factor beta 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.
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.
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.
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.
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ABSTRACT: Introduction In this study, patients suspected of having a clinical diagnosis of Marfan Syndrome (MFS), Loeys-Dietz Syndrome (LDS) and Thoracic Aortic Aneurysms and dissections (TAAD) were referred for genetic testing and examined for mutations in the FBN1, TGFβR1, TGFβR2 and ACTA2 genes. Methods We examined 594 samples from unrelated individuals and different combinations of genes were sequenced, including one or more of the following: FBN1, TGFβR1, TGFβR2, ACTA2, and, in some cases, FBN1 was analyzed by MLPA to detect large deletions. Results A total of 112 patients had a positive result. Of those, 61 had a clinical diagnosis of MFS, eight had LDS, three had TAAD and 40 patients had clinical features with no specific diagnosis provided. A total of 44 patients had an inconclusive result; 12 patients were referred with a clinical diagnosis of MFS, 4 with LDS and 9 with TAAD and 19 had no clinical diagnosis. A total of 89 mutations were novel. Conclusion This study reveals the rate of detection of variants in several genes associated with MFS, LDS and TAAD. The evaluation of patients by individuals with expertise in the field may decrease the likelihood of ordering unnecessary molecular testing. Nevertheless, genetic testing supports the diagnosis of MFS, LDS and TAAD.Molecular Genetics and Metabolism 06/2014; 112(2). DOI:10.1016/j.ymgme.2014.03.011 · 2.83 Impact Factor
Conference Paper: Collision resolution in pseudocellular WLANs with beamforming[Show abstract] [Hide abstract]
ABSTRACT: The paper provides a technique that can successfully recover data when collision occurs in pseudocellular wireless local area networks (WLANs). Pseudocellular WLANs use beamforming at the access point (AP). Mobile users send multiple data packets at the same time using different signature waveforms as in CDMA cellular network. Each user randomly chooses a signature waveform during the contention frame. If the same signature waveforms is selected by more than one user, a collision occurs. The proposed successive multiuser detection scheme with orthogonal ID sequence design enables the system to recover the data from collision. This helps to prevent mobile users from starting back-off timing due to failure in contention for the channel. Hence the total delay is lowered and the capacity of the system improves by a large amount under heavy traffic.Control, Communications and Signal Processing, 2004. First International Symposium on; 02/2004
- Angiología 01/2010; 62(1):42-42. DOI:10.1016/S0003-3170(10)70012-2