Search

Your search keyword '"Verstraeten, A (Aline)"' showing total 5 results
Start Over Author "Verstraeten, A (Aline)"
5 results on '"Verstraeten, A (Aline)"'

1. Copy number variation analysis in bicuspid aortic valve-related aortopathy identifies TBX20 as a contributing gene

Author

Luyckx, I, Kumar, AA, Reyniers, E, Dekeyser, E, Vanderstraeten, K, Vandeweyer, G, Wunnemann, F, Preuss, C, Mazzella, JM, Goudot, G, Messas, E, Albuisson, J, Jeunemaitre, X, Eriksson, P, Mohamed, SA, Kempers, M, Salemink, S, Duijnhouwer, A, Andelfinger, G, Dietz, HC, Verstraeten, A (Aline), Van Laer, L, Loeys, BL, Zhurayev, R, Zerbino, D, Mital, S, Mertens, L, Franco-Cereceda, A, Verhagen, Judith, De Graaf - van de Laar, Ingrid, Wessels, Marja, Nemcikova, M, Krebsova, A, Clinical Genetics, MIBAVA Leducq Consortium, Goudot, Guillaume, University of Antwerp (UA), Centre de recherche du CHU Sainte-Justine / Research Center of the Sainte-Justine University Hospital [Montreal, Canada], Université de Montréal (UdeM)-CHU Sainte Justine [Montréal], The Jackson Laboratory [Bar Harbor] (JAX), Centre de Réféfence des Maladies Vasculaires Rares [HEGP, APHP] (CRMVR), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5), Karolinska Institutet [Stockholm], Karolinska University Hospital [Stockholm], University Medical Center of Schleswig–Holstein = Universitätsklinikum Schleswig-Holstein (UKSH), Kiel University, Radboud University Medical Center [Nijmegen], Howard Hughes Medical Institute (HHMI), Johns Hopkins University School of Medicine [Baltimore], and MIBAVA Leducq Consortium: Rustam Zhurayev, Dmytro Zerbino, Seema Mital, Luc Mertens, Anders Franco-Cereceda, Judith M A Verhagen, Ingrid M B H van de Laar, Marja W Wessels, Michaela Nemcikova, Alice Krebsova

Subjects
Adult, Heart Defects, Congenital, Male, Candidate gene, DNA Copy Number Variations, [SDV]Life Sciences [q-bio], Vascular damage Radboud Institute for Health Sciences [Radboudumc 16], Population, Heart Valve Diseases, Genome-wide association study, Disease, complex mixtures, Article, 03 medical and health sciences, Aortic aneurysm, All institutes and research themes of the Radboud University Medical Center, Bicuspid aortic valve, Bicuspid Aortic Valve Disease, Databases, Genetic, parasitic diseases, Genetics, medicine, Humans, Copy-number variation, education, Biology, Genetics (clinical), 0303 health sciences, education.field_of_study, Aortic Aneurysm, Thoracic, business.industry, 030305 genetics & heredity, Middle Aged, medicine.disease, Phenotype, digestive system diseases, [SDV] Life Sciences [q-bio], Chemistry, Aortic Valve, Female, Human medicine, T-Box Domain Proteins, business, Genome-Wide Association Study, Rare cancers Radboud Institute for Health Sciences [Radboudumc 9]
Abstract

International audience; Bicuspid aortic valve (BAV) is the most common congenital heart defect (CHD), affecting 1-2% of the population. BAV is associated with thoracic aortic aneurysms (TAAs). Deleterious copy number variations (CNVs) were found previously in up to 10% of CHD cases. This study aimed at unravelling the contribution of deleterious deletions or duplications in 95 unrelated BAV/TAA patients. Seven unique or rare CNVs were validated, harbouring protein-coding genes with a role in the cardiovascular system. Based on the presence of overlapping CNVs in patients with cardiovascular phenotypes in the DECIPHER database, the identification of similar CNVs in whole-exome sequencing data of 67 BAV/TAA patients and suggested topological domain involvement from Hi-C data, supportive evidence was obtained for two genes (DGCR6 and TBX20) of the seven initially validated CNVs. A rare variant burden analysis using next-generation sequencing data from 637 BAV/TAA patients was performed for these two candidate genes. This revealed a suggestive genetic role for TBX20 in BAV/TAA aetiology, further reinforced by segregation of a rare TBX20 variant with the phenotype within a BAV/TAA family. To conclude, our results do not confirm a significant contribution for deleterious CNVs in BAV/TAA as only one potentially pathogenic CNV (1.05%) was identified. We cannot exclude the possibility that BAV/TAA is occasionally attributed to causal CNVs though, or that certain CNVs act as genetic risk factors by creating a sensitised background for BAV/TAA. Finally, accumulative evidence for TBX20 involvement in BAV/TAA aetiology underlines the importance of this transcription factor in cardiovascular disease.

Published
2019
Full Text
View/download PDF

2. A mutation update on the LDS-associated genes TGFB2/3 and SMAD2/3

Author

Schepers, D, Tortora, G, Morisaki, H, MacCarrick, G, Lindsay, M, Liang, D, Mehta, SG, Hague, J, Verhagen, Judith, De Graaf - van de Laar, Ingrid, Wessels, Marja, Detisch, Y, van Haelst, M, Baas, A, Lichtenbelt, K, Braun, K, Linde, Denise, Roos - Hesselink, Jolien, McGillivray, G, Meester, J, Maystadt, I, Coucke, P, El-Khoury, E, Parkash, S, Diness, B, Risom, L, Scurr, I, Hilhorst-Hofstee, Y, Morisaki, T, Richer, J, Desir, J, Kempers, M, Rideout, AL, Horne, G, Bennett, C, Rahikkala, E, Vandeweyer, G, Alaerts, M, Verstraeten, A (Aline), Dietz, H, Van Laer, L, Loeys, B, Schepers, D, Tortora, G, Morisaki, H, MacCarrick, G, Lindsay, M, Liang, D, Mehta, SG, Hague, J, Verhagen, Judith, De Graaf - van de Laar, Ingrid, Wessels, Marja, Detisch, Y, van Haelst, M, Baas, A, Lichtenbelt, K, Braun, K, Linde, Denise, Roos - Hesselink, Jolien, McGillivray, G, Meester, J, Maystadt, I, Coucke, P, El-Khoury, E, Parkash, S, Diness, B, Risom, L, Scurr, I, Hilhorst-Hofstee, Y, Morisaki, T, Richer, J, Desir, J, Kempers, M, Rideout, AL, Horne, G, Bennett, C, Rahikkala, E, Vandeweyer, G, Alaerts, M, Verstraeten, A (Aline), Dietz, H, Van Laer, L, and Loeys, B

Published
2018

3. Candidate gene resequencing in a large bicuspid aortic valve-associated thoracic aortic aneurysm cohort: SMAD6 as an important contributor

Author

Gillis, E. (Elisabeth), Kumar, A.A. (Ajay A.), Luyckx, I. (Ilse), Preuss, C. (Christoph), Cannaerts, E. (Elyssa), Beek, G. (Gerarda van de), Wieschendorf, B. (Björn), Alaerts, M. (Maaike), Bolar, N. (Nikhita), Vandeweyer, G. (Geert), Meester, J. (Josephina), Wünnemann, F. (Florian), Gould, R.A. (Russell A.), Zhurayev, R. (Rustam), Zerbino, D. (Dmytro), Mohamed, S.A. (Salah A.), Mital, S. (Seema), Mertens, L. (Luc), Björck, H.M. (Hanna M.), Franco-Cereceda, A. (Anders), McCallion, A.S. (Andrew), Laer, L. (Lut) van, Verhagen, J.M.A. (Judith), Laar, I.M.B.H. (Ingrid) van de, Wessels, M.W. (Marja), Messas, E. (Emmanuel), Goudot, G. (Guillaume), Nemcikova, M. (Michaela), Krebsova, A. (Alice), Kempers, M.J.E. (Marlies), Salemink, S. (Simone), Duijnhouwer, T. (Toon), Jeunemaître, X. (Xavier), Albuisson, J. (Juliette), Eriksson, P. (Per), Andelfinger, G. (Gregor), Dietz, H.C. (Harry ), Verstraeten, A. (Aline), Loeys, B.L. (Bart), Gillis, E. (Elisabeth), Kumar, A.A. (Ajay A.), Luyckx, I. (Ilse), Preuss, C. (Christoph), Cannaerts, E. (Elyssa), Beek, G. (Gerarda van de), Wieschendorf, B. (Björn), Alaerts, M. (Maaike), Bolar, N. (Nikhita), Vandeweyer, G. (Geert), Meester, J. (Josephina), Wünnemann, F. (Florian), Gould, R.A. (Russell A.), Zhurayev, R. (Rustam), Zerbino, D. (Dmytro), Mohamed, S.A. (Salah A.), Mital, S. (Seema), Mertens, L. (Luc), Björck, H.M. (Hanna M.), Franco-Cereceda, A. (Anders), McCallion, A.S. (Andrew), Laer, L. (Lut) van, Verhagen, J.M.A. (Judith), Laar, I.M.B.H. (Ingrid) van de, Wessels, M.W. (Marja), Messas, E. (Emmanuel), Goudot, G. (Guillaume), Nemcikova, M. (Michaela), Krebsova, A. (Alice), Kempers, M.J.E. (Marlies), Salemink, S. (Simone), Duijnhouwer, T. (Toon), Jeunemaître, X. (Xavier), Albuisson, J. (Juliette), Eriksson, P. (Per), Andelfinger, G. (Gregor), Dietz, H.C. (Harry ), Verstraeten, A. (Aline), and Loeys, B.L. (Bart)

Abstract

Bicuspid aortic valve (BAV) is the most common congenital heart defect. Although many BAV patients remain asymptomatic, at least 20% develop thoracic aortic aneurysm (TAA). Historically, BAV-related TAA was considered as a hemodynamic consequence of the valve defect. Multiple lines of evidence currently suggest that genetic determinants contribute to the pathogenesis of both BAV and TAA in affected individuals. Despite high heritability, only very few genes have been linked to BAV or BAV/TAA, such as NOTCH1, SMAD6, and MAT2A. Moreover, they only explain a minority of patients. Other candidate genes have been suggested based on the presence of BAV in knockout mouse models (e.g., GATA5, NOS3) or in syndromic (e.g., TGFBR1/2, TGFB2/3) or non-syndromic (e.g., ACTA2) TAA forms. We hypothesized that rare genetic variants in these genes may be enriched in patients presenting with both BAV and TAA. We performed targeted resequencing of 22 candidate genes using Haloplex target enrichment in a strictly defined BAV/TAA cohort (n = 441; BAV in addition to an aortic root or ascendens diameter = 4.0 cm in adults, or a Z-score = 3 in children) and in a collection of healthy controls with normal echocardiographic evaluation (n = 183). After additional burden analysis against the Exome Aggregation Consortium database, the strongest candidate susceptibility gene was SMAD6 (p = 0.002), with 2.5% (n = 11) of BAV/TAA patients harboring causal variants, including two nonsense, one in-frame deletion and two frameshift mutations. All six missense mutations were located in the functionally important MH1 and MH2 domains. In conclusion, we report a significant contribution of SMAD6 mutations to the etiology of the BAV/TAA phenotype.

Published
2017
Full Text
View/download PDF

4. Corrigendum: Candidate gene resequencing in a large bicuspid aortic valve-associated thoracic aortic aneurysm cohort: SMAD6 as an important contributor [Front. Physiol, 8, (2017) (400)] doi: 10.3389/fphys.2017.00400

Author

Gillis, E. (Elisabeth), Kumar, A.A. (Ajay A.), Luyckx, I. (Ilse), Preuss, C. (Christoph), Cannaerts, E. (Elyssa), Van De Beek, G. (Gerarda), Wieschendorf, B. (Björn), Alaerts, M. (Maaike), Bolar, N. (Nikhita), Vandeweyer, G. (Geert), Meester, J. (Josephina), Wünnemann, F. (Florian), Gould, R.A. (Russell A.), Zhurayev, R. (Rustam), Zerbino, D. (Dmytro), Mohamed, S.A. (Salah A.), Mital, S. (Seema), Mertens, L. (Luc), Björck, H.M. (Hanna M.), Franco-Cereceda, A. (Anders), McCallion, A.S. (Andrew), Van Laer, L. (Lut), Verhagen, J.M.A. (Judith), van de Laar, I.M.B.H. (Ingrid M.B.H.), Wessels, M.W. (Marja), Messas, E. (Emmanuel), Goudot, G. (Guillaume), Nemcikova, M. (Michaela), Krebsova, A. (Alice), Kempers, M.J.E. (Marlies), Salemink, S. (Simone), Duijnhouwer, T. (Toon), Jeunemaître, X. (Xavier), Albuisson, J. (Juliette), Eriksson, P. (Per), Andelfinger, G. (Gregor), Dietz, H.C. (Harry ), Verstraeten, A. (Aline), Loeys, B.L. (Bart), Gillis, E. (Elisabeth), Kumar, A.A. (Ajay A.), Luyckx, I. (Ilse), Preuss, C. (Christoph), Cannaerts, E. (Elyssa), Van De Beek, G. (Gerarda), Wieschendorf, B. (Björn), Alaerts, M. (Maaike), Bolar, N. (Nikhita), Vandeweyer, G. (Geert), Meester, J. (Josephina), Wünnemann, F. (Florian), Gould, R.A. (Russell A.), Zhurayev, R. (Rustam), Zerbino, D. (Dmytro), Mohamed, S.A. (Salah A.), Mital, S. (Seema), Mertens, L. (Luc), Björck, H.M. (Hanna M.), Franco-Cereceda, A. (Anders), McCallion, A.S. (Andrew), Van Laer, L. (Lut), Verhagen, J.M.A. (Judith), van de Laar, I.M.B.H. (Ingrid M.B.H.), Wessels, M.W. (Marja), Messas, E. (Emmanuel), Goudot, G. (Guillaume), Nemcikova, M. (Michaela), Krebsova, A. (Alice), Kempers, M.J.E. (Marlies), Salemink, S. (Simone), Duijnhouwer, T. (Toon), Jeunemaître, X. (Xavier), Albuisson, J. (Juliette), Eriksson, P. (Per), Andelfinger, G. (Gregor), Dietz, H.C. (Harry ), Verstraeten, A. (Aline), and Loeys, B.L. (Bart)

Abstract

In the original article, we noted two mutation annotation errors. The correction of these two mistakes does not change the scientific conclusions in any way. The authors apologize for these nomenclature errors. Please find below the corrected annotations of those two mutations: (1) The correct RNA and protein annotations of the SMAD6 variant in P99 are c.455_461del and p.Pro152Profs*27, and not c.454_461del and p.Gly166Valfs*23. (2) The correct RNA and protein annotations of the SMAD6 variant in P128 are c.74_79del and p.Ser27_Gly28del, and not c.73_79del and p.Gly26_Ser27del. As a consequence, a correction has been made to RESULTS, Paragraphs 5 and 6: The SMAD6 c.726del variant leads to a frameshift (p.Lys242Asnfs*300) and a predicted protein with a C-terminal extension due to loss of the intended stop codon. The c.455_461del frameshift variant (p.Pro152Profs*27) causes the introduction of a premature stop codon, most likely resulting in haploinsufficiency due to nonsense-mediated mRNA decay (NMD). Also the two nonsense variants (p.Tyr279* and p.Tyr288*) are predicted to lead to NMD. All of the missense variants cluster in the functionally important MH1 and MH2 domains (Makkar et al., 2009) (amino acids 148-275 and 331-496, respectively), which is not the case for the sole missense variant (p.Ser130Leu) found in a control individual (Figure 2). All but one (p.Arg443His) of the identified variants were absent in the ExAC control cohort (v0.3.1; Supplementary Table 2). Moreover, the missense variants in the patient cohort (7/7) are enriched in the MH1 and MH2 domains when compared to ExAC controls (n = 228/430; p = 0.02).

Published
2017
Full Text
View/download PDF

5. Candidate Gene Resequencing in a Large Bicuspid Aortic Valve-Associated Thoracic Aortic Aneurysm Cohort: SMAD6 as an Important Contributor

Author

Gillis, E, Kumar, AA, Luyckx, I, Preuss, C, Cannaerts, E, van de Beek, G, Wieschendorf, B, Alaerts, M, Bolar, N, Vandeweyer, G, Meester, J, Wunnemann, F, Gould, RA, Zhurayev, R, Zerbino, D, Mohamed, SA, Mital, S, Mertens, L, Bjorck, HM, Franco-Cereceda, A, McCallion, AS, Van Laer, L, Verhagen, Judith, De Graaf - van de Laar, Ingrid, Wessels, Marja, Messas, E, Goudot, G, Nemcikova, M, Krebsova, A, Kempers, M, Salemink, S, Duijnhouwer, T, Jeunemaitre, X, Albuisson, J, Eriksson, P, Andelfinger, G, Dietz, HC, Verstraeten, A (Aline), Loeys, BL, Gillis, E, Kumar, AA, Luyckx, I, Preuss, C, Cannaerts, E, van de Beek, G, Wieschendorf, B, Alaerts, M, Bolar, N, Vandeweyer, G, Meester, J, Wunnemann, F, Gould, RA, Zhurayev, R, Zerbino, D, Mohamed, SA, Mital, S, Mertens, L, Bjorck, HM, Franco-Cereceda, A, McCallion, AS, Van Laer, L, Verhagen, Judith, De Graaf - van de Laar, Ingrid, Wessels, Marja, Messas, E, Goudot, G, Nemcikova, M, Krebsova, A, Kempers, M, Salemink, S, Duijnhouwer, T, Jeunemaitre, X, Albuisson, J, Eriksson, P, Andelfinger, G, Dietz, HC, Verstraeten, A (Aline), and Loeys, BL

Published
2017

Catalog

Books, media, physical & digital resources
See catalog results