Novel lox variants in five families with aortic/arterial aneurysm and dissection with variable connective tissue findings

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Standard

Novel lox variants in five families with aortic/arterial aneurysm and dissection with variable connective tissue findings. / Van Gucht, Ilse; Krebsova, Alice; Diness, Birgitte Rode; Laga, Steven; Adlam, Dave; Kempers, Marlies; Samani, Nilesh J.; Webb, Tom R.; Baranowska, Ania A.; Van Den Heuvel, Lotte; Perik, Melanie; Luyckx, Ilse; Peeters, Nils; Votypka, Pavel; Macek, Milan; Meester, Josephina; Van Laer, Lut; Verstraeten, Aline; Loeys, Bart L.

I: International Journal of Molecular Sciences, Bind 22, Nr. 13, 7111, 2021.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Harvard

Van Gucht, I, Krebsova, A, Diness, BR, Laga, S, Adlam, D, Kempers, M, Samani, NJ, Webb, TR, Baranowska, AA, Van Den Heuvel, L, Perik, M, Luyckx, I, Peeters, N, Votypka, P, Macek, M, Meester, J, Van Laer, L, Verstraeten, A & Loeys, BL 2021, 'Novel lox variants in five families with aortic/arterial aneurysm and dissection with variable connective tissue findings', International Journal of Molecular Sciences, bind 22, nr. 13, 7111. https://doi.org/10.3390/ijms22137111

APA

Van Gucht, I., Krebsova, A., Diness, B. R., Laga, S., Adlam, D., Kempers, M., Samani, N. J., Webb, T. R., Baranowska, A. A., Van Den Heuvel, L., Perik, M., Luyckx, I., Peeters, N., Votypka, P., Macek, M., Meester, J., Van Laer, L., Verstraeten, A., & Loeys, B. L. (2021). Novel lox variants in five families with aortic/arterial aneurysm and dissection with variable connective tissue findings. International Journal of Molecular Sciences, 22(13), [7111]. https://doi.org/10.3390/ijms22137111

Vancouver

Van Gucht I, Krebsova A, Diness BR, Laga S, Adlam D, Kempers M o.a. Novel lox variants in five families with aortic/arterial aneurysm and dissection with variable connective tissue findings. International Journal of Molecular Sciences. 2021;22(13). 7111. https://doi.org/10.3390/ijms22137111

Author

Van Gucht, Ilse ; Krebsova, Alice ; Diness, Birgitte Rode ; Laga, Steven ; Adlam, Dave ; Kempers, Marlies ; Samani, Nilesh J. ; Webb, Tom R. ; Baranowska, Ania A. ; Van Den Heuvel, Lotte ; Perik, Melanie ; Luyckx, Ilse ; Peeters, Nils ; Votypka, Pavel ; Macek, Milan ; Meester, Josephina ; Van Laer, Lut ; Verstraeten, Aline ; Loeys, Bart L. / Novel lox variants in five families with aortic/arterial aneurysm and dissection with variable connective tissue findings. I: International Journal of Molecular Sciences. 2021 ; Bind 22, Nr. 13.

Bibtex

@article{5112b95c9d1d40eca52b1ca66b2cd0df,
title = "Novel lox variants in five families with aortic/arterial aneurysm and dissection with variable connective tissue findings",
abstract = "Thoracic aortic aneurysm and dissection (TAAD) is a major cause of cardiovascular morbidity and mortality. Loss-of-function variants in LOX, encoding the extracellular matrix crosslinking enzyme lysyl oxidase, have been reported to cause familial TAAD. Using a next-generation TAAD gene panel, we identified five additional probands carrying LOX variants, including two missense variants affecting highly conserved amino acids in the LOX catalytic domain and three truncating variants. Connective tissue manifestations are apparent in a substantial fraction of the variant carriers. Some LOX variant carriers presented with TAAD early in life, while others had normal aortic diam-eters at an advanced age. Finally, we identified the first patient with spontaneous coronary artery dissection carrying a LOX variant. In conclusion, our data demonstrate that loss-of-function LOX variants cause a spectrum of aortic and arterial aneurysmal disease, often combined with connective tissue findings.",
keywords = "ECM, LDS, LOX, MFS, TAAD",
author = "{Van Gucht}, Ilse and Alice Krebsova and Diness, {Birgitte Rode} and Steven Laga and Dave Adlam and Marlies Kempers and Samani, {Nilesh J.} and Webb, {Tom R.} and Baranowska, {Ania A.} and {Van Den Heuvel}, Lotte and Melanie Perik and Ilse Luyckx and Nils Peeters and Pavel Votypka and Milan Macek and Josephina Meester and {Van Laer}, Lut and Aline Verstraeten and Loeys, {Bart L.}",
note = "Funding Information: This research was largely supported by funding from the University of Antwerp (Methusalem- OEC grant ?Genomed? FFB190208), the Research Foundation Flanders (FWO, Belgium, G042321N, G040221N, G044720N), the Dutch Heart Foundation (2013T093), the Belgian Cardiac Surgery Foundation and the Marfan Foundation. Dr. Loeys holds a consolidator grant from the European Research Council (Genomia?ERC-COG-2017-771945). Dr. Meester (12X8520N) is post-doctoral FWO fellowsMs. Van Gucht (1S70419N),Ms. Van Den Heuvel (1S81820N) are supported by an FWO PhD fellowship. Dr. Loeys, Dr. Verstraeten and Dr. Kempers are members of the European Reference Network on rare multisystemic vascular disorders (VASCERN?project ID: 769036 partly co-funded by the European Union Third Health Programme). The UK SCAD study was supported by BeatSCAD, the British Heart Foundation (BHF) PG/13/96/30608, the NIHR rare disease translational collaboration and the Leicester NIHR Biomedical Research Centre. Dave Adlam has received funding from Abbott Vascular Inc to support a clinical research fellow, in kind support for SCAD-genetics research from Astra Zeneca Inc and research funding from the same company for unrelated research. He has undertaken consultancy for General Electric Inc to support general research funds. Supported by Ministry of Health of the Czech Republic, grant nr. NV18-02-00237 and 00064203/6003 to M.M and A.K. Publisher Copyright: {\textcopyright} 2021 by the authors. Licensee MDPI, Basel, Switzerland.",
year = "2021",
doi = "10.3390/ijms22137111",
language = "English",
volume = "22",
journal = "International Journal of Molecular Sciences (Online)",
issn = "1661-6596",
publisher = "MDPI AG",
number = "13",

}

RIS

TY - JOUR

T1 - Novel lox variants in five families with aortic/arterial aneurysm and dissection with variable connective tissue findings

AU - Van Gucht, Ilse

AU - Krebsova, Alice

AU - Diness, Birgitte Rode

AU - Laga, Steven

AU - Adlam, Dave

AU - Kempers, Marlies

AU - Samani, Nilesh J.

AU - Webb, Tom R.

AU - Baranowska, Ania A.

AU - Van Den Heuvel, Lotte

AU - Perik, Melanie

AU - Luyckx, Ilse

AU - Peeters, Nils

AU - Votypka, Pavel

AU - Macek, Milan

AU - Meester, Josephina

AU - Van Laer, Lut

AU - Verstraeten, Aline

AU - Loeys, Bart L.

N1 - Funding Information: This research was largely supported by funding from the University of Antwerp (Methusalem- OEC grant ?Genomed? FFB190208), the Research Foundation Flanders (FWO, Belgium, G042321N, G040221N, G044720N), the Dutch Heart Foundation (2013T093), the Belgian Cardiac Surgery Foundation and the Marfan Foundation. Dr. Loeys holds a consolidator grant from the European Research Council (Genomia?ERC-COG-2017-771945). Dr. Meester (12X8520N) is post-doctoral FWO fellowsMs. Van Gucht (1S70419N),Ms. Van Den Heuvel (1S81820N) are supported by an FWO PhD fellowship. Dr. Loeys, Dr. Verstraeten and Dr. Kempers are members of the European Reference Network on rare multisystemic vascular disorders (VASCERN?project ID: 769036 partly co-funded by the European Union Third Health Programme). The UK SCAD study was supported by BeatSCAD, the British Heart Foundation (BHF) PG/13/96/30608, the NIHR rare disease translational collaboration and the Leicester NIHR Biomedical Research Centre. Dave Adlam has received funding from Abbott Vascular Inc to support a clinical research fellow, in kind support for SCAD-genetics research from Astra Zeneca Inc and research funding from the same company for unrelated research. He has undertaken consultancy for General Electric Inc to support general research funds. Supported by Ministry of Health of the Czech Republic, grant nr. NV18-02-00237 and 00064203/6003 to M.M and A.K. Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

PY - 2021

Y1 - 2021

N2 - Thoracic aortic aneurysm and dissection (TAAD) is a major cause of cardiovascular morbidity and mortality. Loss-of-function variants in LOX, encoding the extracellular matrix crosslinking enzyme lysyl oxidase, have been reported to cause familial TAAD. Using a next-generation TAAD gene panel, we identified five additional probands carrying LOX variants, including two missense variants affecting highly conserved amino acids in the LOX catalytic domain and three truncating variants. Connective tissue manifestations are apparent in a substantial fraction of the variant carriers. Some LOX variant carriers presented with TAAD early in life, while others had normal aortic diam-eters at an advanced age. Finally, we identified the first patient with spontaneous coronary artery dissection carrying a LOX variant. In conclusion, our data demonstrate that loss-of-function LOX variants cause a spectrum of aortic and arterial aneurysmal disease, often combined with connective tissue findings.

AB - Thoracic aortic aneurysm and dissection (TAAD) is a major cause of cardiovascular morbidity and mortality. Loss-of-function variants in LOX, encoding the extracellular matrix crosslinking enzyme lysyl oxidase, have been reported to cause familial TAAD. Using a next-generation TAAD gene panel, we identified five additional probands carrying LOX variants, including two missense variants affecting highly conserved amino acids in the LOX catalytic domain and three truncating variants. Connective tissue manifestations are apparent in a substantial fraction of the variant carriers. Some LOX variant carriers presented with TAAD early in life, while others had normal aortic diam-eters at an advanced age. Finally, we identified the first patient with spontaneous coronary artery dissection carrying a LOX variant. In conclusion, our data demonstrate that loss-of-function LOX variants cause a spectrum of aortic and arterial aneurysmal disease, often combined with connective tissue findings.

KW - ECM

KW - LDS

KW - LOX

KW - MFS

KW - TAAD

U2 - 10.3390/ijms22137111

DO - 10.3390/ijms22137111

M3 - Journal article

C2 - 34281165

AN - SCOPUS:85111866564

VL - 22

JO - International Journal of Molecular Sciences (Online)

JF - International Journal of Molecular Sciences (Online)

SN - 1661-6596

IS - 13

M1 - 7111

ER -

ID: 301821366